I-PRP Yesimanje: “I-PRP Yomtholampilo”
Eminyakeni eyi-10 edlule, uhlelo lokwelapha lwe-PRP lube nezinguquko ezinkulu.Ngocwaningo lokuhlola nolwemitholampilo, manje sesinokuqonda okungcono kwe-platelet kanye nenye i-physiology yamaseli.Ukwengeza, ukuhlolwa okuhlelekile kwekhwalithi ephezulu, ukuhlaziywa kwe-meta kanye nokuhlolwa okulawulwa ngokungahleliwe kubonise ukuphumelela kwe-PRP biotechnology emikhakheni eminingi yezokwelapha, kuhlanganise ne-dermatology, ukuhlinzwa kwenhliziyo, ukuhlinzwa kwepulasitiki, ukuhlinzwa kwamathambo, ukuphathwa kobuhlungu, izifo zomgogodla, kanye nemithi yezemidlalo. .
Isici samanje se-PRP ukugcwala kwayo okuphelele kwe-platelet, eshintsha kusukela encazelweni yokuqala ye-PRP (kuhlanganise nokuhlushwa kwe-platelet ephakeme kunevelu eyisisekelo) kuya ngaphezu kwe-1 × 10 6/µ L noma cishe izikhathi ezi-5 ubuncane bokuhlushwa kwe-platelet kuma-platelet kusuka isisekelo.Ekubuyekezweni okubanzi kukaFadadu et al.Amasistimu we-PRP angu-33 nezinqubo ezilandelwayo zahlolwa.Isibalo se-platelet sokulungiswa kwe-PRP yokugcina ekhiqizwa ezinye zalezi zinhlelo siphansi kunegazi lonke.Babike ukuthi i-platelet factor ye-PRP ikhuphuke njenge-0.52 nge-single spin kit (Selphyl ®).Ngokuphambene, ukujikeleza kabili kwe-EmCyte Genesis PurePRPII ® I-concentration ye-platelet ekhiqizwa idivayisi iphezulu kakhulu (1.6 × 10 6 /µL) .
Ngokusobala, izindlela ze-in vitro nezezilwane aziyona indawo yocwaningo efanelekile yokuguqulwa okuyimpumelelo ekwenziweni komtholampilo.Ngokufanayo, isifundo sokuqhathanisa idivayisi asisekeli isinqumo, ngoba sibonisa ukuthi ukuhlushwa kwe-platelet phakathi kwamadivayisi we-PRP kuhluke kakhulu.Ngenhlanhla, ngobuchwepheshe obusekelwe ku-proteomics nokuhlaziya, singakhulisa ukuqonda kwethu imisebenzi yeseli ku-PRP ethinta imiphumela yokwelashwa.Ngaphambi kokufinyelela ukuvumelana mayelana namalungiselelo e-PRP ajwayelekile kanye nokwakheka, i-PRP kufanele ilandele ukwakheka kwe-PRP yomtholampilo ukukhuthaza izindlela ezinkulu zokulungisa izicubu kanye nemiphumela yomtholampilo eqhubekayo.
Ifomula ye-PRP yomtholampilo
Njengamanje, i-PRP yomtholampilo ephumelelayo (C-PRP) ibonakala njengenhlanganisela eyinkimbinkimbi yezingxenye ze-autologous multicellular ku-plasma yevolumu encane etholakala engxenyeni yegazi le-peripheral ngemva kwe-centrifugation.Ngemuva kwe-centrifugation, i-PRP kanye nezingxenye zayo zeseli ezingezona i-platelet zingatholwa kusukela kudivayisi yokuhlushwa ngokuya ngokuminyana kwamaseli ahlukene (lapho ukuminyana kweplatelet kuphansi kakhulu).
Sebenzisa imishini yokuhlukanisa i-PurePRP-SP ® Cell density (EmCyte Corporation, Fort Myers, FL, USA) yasetshenziselwa igazi lonke ngemva kwezinqubo ezimbili ze-centrifugation.Ngemva kwenqubo yokuqala ye-centrifugation, yonke ingxenye yegazi yahlukaniswa yaba izingqimba ezimbili eziyisisekelo, ukumiswa kwe-platelet (lean) plasma kanye nongqimba lwamangqamuzana egazi abomvu.Ku-A, isinyathelo sesibili se-centrifugation sesiqediwe.Ivolumu yangempela ye-PRP ingakhishwa ukuze kusetshenziswe isiguli.Ukukhulisa ku-B kukhombisa ukuthi kukhona ungqimba olunsundu olunezingxenye eziningi ze-erythrocyte sedimentation (elimelwe umugqa oluhlaza) ezansi kwemishini, equkethe ukugxila okuphezulu kwamaplatelet, ama-monocyte nama-lymphocyte, asuselwa ku-density gradient.Kulesi sibonelo, ngokusho kwe-C-PRP yokulungiselela iphrothokholi ene-neutrophils empofu, iphesenti elincane lama-neutrophils (<0.3%) kanye nama-erythrocytes (<0.1%) azokhishwa.
I-Platelet granule
Ekusetshenzisweni kokuqala kwe-PRP yomtholampilo, i-α- Granules iyisakhiwo sangaphakathi seplatelet evame ukucashunwa, ngoba aqukethe izici zokuhlangana, inani elikhulu le-PDGF nezilawuli ze-angiogenic, kodwa anomsebenzi omncane we-thrombogenic.Ezinye izici zihlanganisa izingxenye ze-chemokine ne-cytokine ezaziwa kancane, njenge-platelet factor 4 (PF4), amaprotheni ayisisekelo e-pre-platelet, i-P-selectin (i-activator ye-integrin) kanye ne-chemokine RANTES (elawulwa ngokuvula, eveza amaseli e-T avamile futhi cishe ukufihla).Umsebenzi wonkana walezi zingxenye ezithile ze-platelet granule uwukunxenxa futhi wenze amanye amaseli omzimba asebenze noma ubangele ukuvuvukala kwamaseli e-endothelial.
Izingxenye eziminyene ze-granular ezifana ne-ADP, i-serotonin, i-polyphosphate, i-histamine ne-adrenaline zisetshenziswa ngokusobala kakhulu njengokulawula ukusebenza kweplatelet kanye ne-thrombosis.Okubaluleke kakhulu, eziningi zalezi zakhi zinomsebenzi wokuguqula amangqamuzana omzimba.I-Platelet ADP ibonwa yi-P2Y12ADP receptor kumaseli e-dendritic (DC), ngaleyo ndlela andise i-antigen endocytosis.I-DC (iseli elethula i-antigen) ibaluleke kakhulu ekuqaliseni ukusabela kwamasosha omzimba we-T cell kanye nokulawula ukusabela kokuzivikela komzimba okuvikelayo, okuxhumanisa amasosha omzimba azalwa nawo kanye nesimiso somzimba sokuzivikela ezimweni esiguquguqukayo.Ukwengeza, i-platelet adenosine triphosphate (ATP) ithumela amasignali nge-T cell receptor P2X7, okuholela ekwandeni kokuhlukaniswa kwamaseli angumsizi we-CD4 T abe amaseli e-proinflammatory T umsizi 17 (Th17).Ezinye izingxenye ze-platelet eziminyene ze-granule (ezifana ne-glutamate ne-serotonin) zikhuthaza ukufuduka kwamaseli e-T futhi zikhulise ukuhlukaniswa kwe-monocyte ku-DC, ngokulandelanayo.Ku-PRP, lawa ma-immunomodulators atholakala ezinhlayiyeni eziminyene anothiswe kakhulu futhi anemisebenzi eminingi yokuzivikela komzimba.
Inani lokusebenzelana okungaba khona okuqondile nokungaqondile phakathi kwamaplatelet namanye (ama-receptor) amaseli libanzi.Ngakho-ke, ukusetshenziswa kwe-PRP endaweni yendawo yezicubu ze-pathological kungabangela imiphumela ehlukahlukene yokuvuvukala.
Ukugxila kwe-platelet
I-C-PRP kufanele iqukathe imithamo yomtholampilo yamaplatelet agxilile ukuze akhiqize imiphumela yokwelapha enenzuzo.Ama-platelets ku-C-PRP kufanele akhuthaze ukwanda kwamangqamuzana, ukuhlanganiswa kwezici ze-mesenchymal kanye ne-neurotrophic, akhuthaze ukufuduka kwamangqamuzana e-chemotactic futhi akhuthaze umsebenzi we-immunoregulatory, njengoba kuboniswe esithombeni.
Ama-platelet acushiwe, ukukhululwa kwe-PGF nama-adhesion molecules kulamula ukusebenzisana kwamaseli okuhlukahlukene: i-chemotaxis, ukunamathela kwamaseli, ukufuduka, nokuhlukaniswa kwamaseli, futhi kulawula imisebenzi yokulawula amasosha omzimba.Lokhu kusebenzisana kwe-platelet cell-cell kunomthelela ku-angiogenesis kanye nomsebenzi wokuvuvukala, futhi ekugcineni kukhuthaze inqubo yokulungisa izicubu.Izifinyezo: i-BMA: i-bone marrow aspirate, i-EPC: amaseli e-endothelial progenitor, i-EC: amaseli e-endothelial, i-5-HT: i-5-hydroxytryptamine, i-RANTES: ukulawulwa okucushiwe kokuvezwa kwe-T cell okujwayelekile kanye nokukhishwa kwe-putive, i-JAM: uhlobo lwe-molecule ye-adhesion, i-CD40L: iqoqo I-40 ligand, SDF-1 α: I-Stromal cell-derived factor-1 α, CXCL: chemokine (CXC motif) ligand, PF4: i-platelet factor 4. Ithathwe ku-Everts et al.
UMarx wayengumuntu wokuqala ukufakazela ukuthi ukuphulukiswa kwethambo nezicubu ezithambile kwathuthukiswa, futhi inani elincane leplatelet lalingu-1 × 10 6 /µL. Le miphumela yaqinisekiswa ocwaningweni lokuhlangana kwe-lumbar ngokusebenzisa i-intervertebral foramen, lapho umthamo weplatelet wawumkhulu 1.3 × Ku-106 platelet/µ L, lolu cwaningo lubonise ukuhlangana okwengeziwe.Ngaphezu kwalokho, uGiusti et al.Kwembulwe 1.5 × Indlela yokulungisa izicubu ngethamo elingu-109 idinga amaplatelet/mL ukuze ifake i-angiogenesis esebenzayo ngomsebenzi weseli endothelial.Ocwaningweni lwakamuva, ukugxila okuphezulu kwehlise amandla e-angiogenesis amaplatelet ngaphakathi nasezindaweni ezizungezile.Ukwengeza, idatha yangaphambilini ibonise ukuthi umthamo we-PRP uzophinde uthinte imiphumela yokwelashwa.Ngakho-ke, ukuze kubangele kakhulu ukusabela kwe-angiogenesis futhi kukhuthaze ukwanda kwamaseli kanye nokufuduka kwamaseli, i-C-PRP kufanele iqukathe okungenani i-7.5 ebhodleleni lokwelapha le-5-mL le-PRP × 10 9 ingaletha amaplatelet.
Ngaphezu kokuncika komthamo, umphumela we-PRP emsebenzini weseli ubonakala uncike kakhulu esikhathini.USophie et al.Le miphumela iphakamisa ukuthi ukuchayeka kwesikhashana kuma-platelet lysate abantu kungashukumisa ukwanda kwamangqamuzana amathambo kanye ne-chemotaxis.Ngokuphambene nalokho, ukuchayeka isikhathi eside ku-PRP kuzoholela emazingeni aphansi e-alkaline phosphatase nokwakheka kwamaminerali.
Ingqamuzana elibomvu legazi
Amangqamuzana abomvu egazi anomthwalo wemfanelo wokuthutha umoya-mpilo ezicutshini futhi adlulisele isikhutha sisuka ezicutshini siye emaphashini.Azinayo i-nucleus futhi zakhiwe ama-molecule e-heme abopha amaprotheni.Izingxenye zensimbi ne-heme emangqamuzaneni abomvu egazi zikhuthaza inhlanganisela yomoya-mpilo nesikhutha.Ngokuvamile, umjikelezo wokuphila kwamangqamuzana abomvu egazi cishe izinsuku eziyi-120.Akhishwa ekujikelezeni kwama-macrophage ngenqubo ebizwa ngokuthi ukuguga kwe-RBC.Amangqamuzana egazi abomvu kumasampuli e-PRP angase onakaliswe ngaphansi kwezimo ze-shear (isibonelo, ukuhlinzwa ukopha igazi lonke, inqubo yokuzivikela komzimba, ukucindezeleka kwe-oxidative noma uhlelo lokuhlushwa lwe-PRP olunganele).Ngakho-ke, i-RBC cell membrane iyabola futhi ikhiphe i-hemoglobin (Hb) enobuthi, elinganiswa nge-plasma free hemoglobin (PFH), i-heme nensimbi.].I-PFH kanye nemikhiqizo yayo yokuwohloka (i-heme nensimbi) ngokuhlanganyela iholela emiphumeleni eyingozi kanye ne-cytotoxic ezicutshini, okuholela ekucindezelekeni kwe-oxidative, ukulahlekelwa kwe-nitric oxide, ukusebenza kwezindlela zokuvuvukala kanye nokuzivikela komzimba.Le miphumela ekugcineni izoholela ekungasebenzi kahle kwe-microcirculation, i-vasoconstriction yendawo kanye nokulimala kwemithambo, kanye nokulimala okukhulu kwezicubu.
Okubaluleke kakhulu ukuthi uma i-RBC equkethe i-C-PRP ilethwa esicutshini, izobangela ukusabela kwendawo okubizwa ngokuthi i-eryptosis, okuzokwenza ukukhululwa kwe-cytokine ephumelelayo ne-macrophage migration inhibitor.Le cytokine ivimbela ukufuduka kwama-monocytes nama-macrophages.Inikeza amasignali anamandla okuvuvukala ezicutshini ezizungezile, ivimbela ukufuduka kwe-stem cell kanye nokwanda kwe-fibroblast, futhi iholela ekungasebenzi kahle kwamangqamuzana endawo.Ngakho-ke, kubalulekile ukunciphisa ukungcoliswa kwe-RBC emalungiselelweni e-PRP.Ngaphezu kwalokho, indima yamangqamuzana abomvu egazi ekuvuseleleni izicubu ayikaze inqunywe.I-C-PRP eyanele ye-centrifugation kanye nenqubo yokulungiselela ngokuvamile izonciphisa noma iqede ngisho nokuba khona kwamangqamuzana abomvu egazi, ngaleyo ndlela igweme imiphumela emibi ye-hemolysis ne-polycythemia.
Ama-leukocyte ku-C-PRP
Ukuba khona kwamangqamuzana amhlophe egazi emalungiselelweni e-PRP kuncike emishinini yokwelapha kanye nohlelo lokulungiselela.Emishini ye-PRP esekelwe ku-plasma, amangqamuzana egazi amhlophe aqedwa ngokuphelele;Kodwa-ke, amangqamuzana egazi amhlophe ayegxile kakhulu ekulungiseleleni i-PRP ungqimba olunsundu lwe-erythrocyte sedimentation.Ngenxa yezindlela zayo zokuzivikela zokuzivikela komzimba kanye nokusingatha, amangqamuzana amhlophe egazi athinta kakhulu i-biology yangaphakathi yezimo zezicubu ezibukhali nezingamahlalakhona.Lezi zici kuzoxoxwa ngazo ngezansi.Ngakho-ke, ukuba khona kwama-leukocyte athile ku-C-PRP kungabangela imiphumela ebalulekile yamaselula nezicubu.Ngokuqondile, amasistimu ahlukene e-PRP erythrocyte sedimentation ensundu-yellow layer asebenzisa izikimu zokulungiselela ezihlukene, ngaleyo ndlela akhiqize ingxenye ehlukene yama-neutrophils, ama-lymphocyte nama-monocyte ku-PRP.Ama-Eosinophils nama-basophil awakwazi ukulinganiswa kumalungiselelo e-PRP ngoba ulwelwesi lwamaseli awo luntekenteke kakhulu ukuze lukwazi ukumelana namandla okucubungula ama-centrifugal.
Ama-neutrophils
Ama-neutrophils angama-leukocyte abalulekile ezindleleni eziningi zokuphulukisa.Lezi zindlela zihlangana namaprotheni e-antimicrobial akhona kuma-platelet ukwenza umgoqo ominyene ngokumelene namagciwane ahlaselayo.Ukuba khona kwama-neutrophils kunqunywa ngokuvumelana nokuhlosiwe kokwelashwa kwe-C-PRP.Amazinga akhulayo okuvuvukala kwezicubu angase adingeke ekunakekelweni kwesilonda esingapheli se-PRP biotherapy noma ezisetshenziswa ezihloselwe ukukhula kwamathambo noma ukuphulukiswa.Okubalulekile, imisebenzi eyengeziwe ye-neutrophil itholakale kumamodeli amaningana, egcizelela indima yabo ekulungiseni i-angiogenesis nokulungisa izicubu.Kodwa-ke, ama-neutrophils nawo angabangela imiphumela eyingozi, ngakho-ke awafaneleki kwezinye izinhlelo zokusebenza.U-Zhou no-Wang bafakazele ukuthi ukusetshenziswa kwe-PRP ecebile kuma-neutrophils kungaholela ekwandeni kwesilinganiso sohlobo lwe-collagen ye-III ukuze uthayiphe i-collagen ye-I, ngaleyo ndlela kwandisa i-fibrosis nokunciphisa amandla e-tendon.Ezinye izici eziyingozi ezixhunywe ama-neutrophils ukukhululwa kwama-cytokines avuvukalayo kanye ne-matrix metalloproteinases (MMPs), engakhuthaza ukuvuvukala kanye ne-catabolism uma kusetshenziswa ezicutshini.
I-leukomonocyte
Ku-C-PRP, ama-lymphocyte e-mononuclear T no-B agxile kakhulu kunanoma yimaphi amanye amangqamuzana egazi amhlophe.Zihlobene eduze ne-cell-mediated cytotoxic adaptive immunity.Ama-lymphocyte angabangela ukusabela kwamangqamuzana ukulwa nokutheleleka futhi avumelane nabahlaseli.Ngaphezu kwalokho, i-T-lymphocyte etholakala kuma-cytokines (i-interferon- γ [IFN- γ] kanye ne-interleukin-4 (IL-4) ithuthukisa ukuhlukaniswa kwama-macrophages. I-Verassar et al. Kufakazelwa ukuthi ama-lymphocyte e-T avamile angakhuthaza ngokungaqondile ukuphulukiswa kwezicubu imodeli yegundane ngokulawula ukuhlukaniswa kwama-monocyte nama-macrophages.
I-Monocyte - iseli lokulungisa elinamandla amaningi
Ngokusho kwedivayisi yokulungiselela i-PRP esetshenzisiwe, ama-monocyte angase aphume noma angabi khona ebhodleleni lokwelapha le-PRP.Ngeshwa, ukusebenza kwabo kanye nekhono labo lokuvuselela akuvamile ukuthi kukhulunywe ngalo ezincwadini.Ngakho-ke, ukunakwa okuncane kukhokhwa kuma-monocyte endleleni yokulungiselela noma ifomula yokugcina.Iqembu le-Monocyte liyi-heterogeneous, lisuka kumangqamuzana okhokho kumnkantsha wamathambo, futhi lithuthelwa ezicutshini ze-peripheral nge-hematopoietic stem cell pathway ngokuya ngokukhuthazwa kwe-microenvironment.Ngesikhathi se-homeostasis nokuvuvukala, ama-monocyte ajikelezayo ashiya umgudu wegazi futhi abuthelwe ezicutshini ezilimele noma ezonakele.Angakwazi ukusebenza njengama-macrophage (M Φ) Amaseli e-Effector noma amaseli omzali.Ama-monocyte, ama-macrophage namaseli e-dendritic amelela i-mononuclear phagocytic system (MPS). Isici esivamile se-MPS ubupulasitiki bephethini yokusho izakhi zofuzo kanye nokunqwabelana okusebenzayo phakathi kwalezi zinhlobo zamaseli.Ezicubu eziwohlokayo, ama-macrophage ahlala endaweni, izici zokukhula ezisebenza endaweni, ama-cytokines ane-pro-inflammatory, amaseli e-apoptotic noma ama-necrotic kanye nemikhiqizo ye-microbial iqala ama-monocyte ukuze ahlukanise ngamaqembu amaseli e-MPS.Ake sithi lapho i-C-PRP equkethe ama-monocyte anesivuno esiphezulu ijojowe endaweni encane yendawo yesifo, ama-monocyte angase ahlukanise abe yi-M Φ Ukuze abangele izinguquko ezinkulu zamangqamuzana.
Ukusuka ku-monocyte kuye ku-M Φ Enqubweni yokuguqulwa, i-M Φ Phenotype ethile.Eminyakeni eyishumi edlule, kuye kwasungulwa imodeli, ehlanganisa i-M Φ Indlela eyinkimbinkimbi yokwenza kusebenze ichazwa njenge-polarization yezifunda ezimbili eziphikisanayo: M Φ Phenotype 1 (M Φ 1, ukuqaliswa kwe-Classic) kanye ne-M Φ Phenotype 2 (M Φ 2, okunye ukwenza kusebenze).I-M Φ 1 ibonakala ngemfihlo ye-cytokine evuthayo (IFN- γ) Futhi i-nitric oxide ukukhiqiza indlela ephumelelayo yokubulala i-pathogen.M Φ I-phenotype iphinde ikhiqize i-vascular endothelial growth factor (VEGF) kanye ne-fibroblast growth factor (FGF).M Φ I-phenotype yakhiwe ngamaseli alwa nokuvuvukala ane-phagocytosis ephezulu.M Φ 2 Khiqiza izingxenye ze-matrix engaphandle kwamaseli, i-angiogenesis nama-chemokines, ne-interleukin 10 (IL-10).Ngaphandle kokuzivikela kwe-pathogen, i-M Φ Ingakwazi futhi ukunciphisa ukuvuvukala futhi ikhuthaze ukulungiswa kwezicubu.Kuyaphawuleka ukuthi i-M Φ 2 ihlukaniswe yaba ngu-M in vitro Φ 2a, M Φ 2b kanye ne-M Φ 2. Kuncike kusisusa.Ukuhumusha nge-vivo kwalezi zinhlobo ezincane kunzima ngoba izicubu zingaqukatha Amaqembu angu-M Φ axubile.Kuyathakazelisa ukuthi ngokusekelwe kuzimpawu zendawo zendawo kanye namazinga e-IL-4, i-proinflammatory M Φ 1 ingaguqulwa ukuze ikhuthaze ukulungiswa kwe-M Φ 2. Kusukela kule datha, kunengqondo ukucabanga ukuthi kukhona ukugxila okuphezulu kwama-monocyte kanye ne-M Φ C-PRP amalungiselelo. zingase zibe negalelo ekulungiseni izicubu ezingcono ngoba zinamandla okulungisa izicubu ezilwa nokuvuvukala kanye nekhono lokudlulisa isignali yamaseli.
Incazelo edidekile yengxenyana yamaseli amhlophe egazi ku-PRP
Ukuba khona kwamangqamuzana egazi amhlophe emabhodleleni okwelapha e-PRP kuncike kudivayisi yokulungiselela i-PRP futhi kungase kube nomehluko omkhulu.Kunezingxabano eziningi mayelana nokuba khona kwama-leukocyte kanye negalelo lawo emikhiqizweni ehlukene ye-PRP (njenge-PRGF, i-P-PRP, i-LP-PRP, i-LR-PRP, i-P-PRF ne-L-PRF) Ekubuyekezweni kwakamuva, okuyisithupha okungahleliwe. izivivinyo ezilawulwayo (izinga lobufakazi 1) kanye nezifundo ezintathu zokuqhathanisa ezingase zibe khona (izinga lobufakazi 2) elibandakanya iziguli ze-1055, okubonisa ukuthi i-LR-PRP ne-LP-PRP inokuphepha okufanayo.Umlobi waphetha ngokuthi ukusabela okubi kwe-PRP kungase kungahambisani ngokuqondile nokuhlushwa kwamangqamuzana egazi amhlophe.Kwesinye isifundo, i-LR-PRP ayizange iguqule i-interleukin yokuvuvukala (IL-1) ku-OA idolo β, IL-6, IL-8 ne-IL-17).Le miphumela isekela umbono wokuthi indima ye-leukocyte emsebenzini we-biological we-PRP ku-vivo ingase ivele ku-crosstalk phakathi kwama-platelet nama-leukocyte.Lokhu kusebenzisana kungakhuthaza i-biosynthesis yezinye izici (ezifana ne-lipoxygen), ezinganciphisa noma zikhuthaze ukuhlehla kokuvuvukala.Ngemva kokukhululwa kokuqala kwama-molecule avuthayo (i-arachidonic acid, i-leukotriene ne-prostaglandin), i-lipoxygen A4 ikhishwa kuma-platelet acushiwe ukuvimbela ukusebenza kwe-neutrophil.Kukule ndawo lapho i-M Φ Phenotype isuka ku-M Φ 1 Shintshela ku-M Φ 2。 Ngaphezu kwalokho, kunobufakazi obandayo bokuthi amangqamuzana ajikelezayo e-mononuclear angahlukana abe izinhlobo ezihlukahlukene zamaseli angewona ama-phagocytic ngenxa yobuningi bawo.
Uhlobo lwe-PRP luzothinta isiko le-MSC.Uma kuqhathaniswa namasampula e-PRP ahlanzekile noma e-PPP, i-LR-PRP ingabangela ukwanda okuphezulu kakhulu komnkantsha osuselwe kuma-MSC (ama-BMMSC), ngokukhululwa okusheshayo nomsebenzi ongcono we-PGF webhayoloji.Zonke lezi zici zifanelekile ekwengezeni ama-monocyte ebhodleleni lokwelapha le-PRP futhi ziqaphela ikhono lawo lokuzivikela komzimba kanye namandla okuhlukanisa.
I-Congenital and adaptive immune regulation ye-PRP
Umsebenzi odume kakhulu we-physiological wamaplatelet ukulawula ukopha.Zinqwabelana endaweni yokulimala kwezicubu kanye nemithambo yegazi eyonakele.Lezi zenzakalo zibangelwa ukuvezwa kwama-interins nama-selectins ashukumisa ukunamathela kwe-platelet nokuhlanganisa.I-endothelium eyonakele iqhubeza phambili le nqubo, futhi i-collagen eveziwe namanye amaprotheni e-matrix e-subendothelial akhuthaza ukusebenza okujulile kwamaplatelet.Kulezi zimo, indima ebalulekile yokusebenzelana phakathi kwe-von Willebrand factor (vWF) ne-glycoprotein (GP), ikakhulukazi i-GP-Ib, ifakazelwe.Ngemuva kokusebenza kweplatelet, iplatelet α-, Dense, lysosome kanye ne-T-granules ilawula i-exocytosis futhi ikhulule okuqukethwe kwayo endaweni engaphandle kwamaseli.
I-Platelet adhesion molecule
Ukuze siqonde kangcono indima ye-PRP ezicutshini ezivuthayo kanye namaplatelet ekuphenduleni kokuzivikela komzimba, kufanele siqonde ukuthi i-platelet surface receptors ehlukene (integrins) kanye nama-molecule e-adhesion junction (JAM) kanye nokusebenzisana kwamaseli kungaqala izinqubo ezibucayi ekugomeni okungaphakathi nokuguquguqukayo.
Ama-Integrin ama-molecule e-cell adhesion surface atholakala ezinhlotsheni zamaseli ahlukahlukene futhi avezwa ngobuningi kuma-platelet.Ama-integrin afaka i-a5b1, i-a6b1, i-a2b1 LFA-2, (GPIa/IIa) ne-aIIbb3 (GPIIb/IIIa).Ngokuvamile, zikhona esimweni sokuhlangana esimile nesiphansi.Ngemva kokwenza kusebenze, bashintshela esimweni sokubopha i-ligand ephezulu.Ama-Integrin anemisebenzi ehlukene kuma-platelet futhi abamba iqhaza ekusebenzelaneni kwama-platelet anezinhlobo eziningana zamangqamuzana egazi amhlophe, amaseli e-endothelial kanye ne-matrix engaphandle.Ngaphezu kwalokho, inkimbinkimbi ye-GP-Ib-V-IX ivezwa kulwelwesi lweplatelet futhi iyisamukeli esiyinhloko sokubopha nge-von vWF.Lokhu kusebenzisana kulamula ukuthintana kokuqala phakathi kwamaplatelet kanye nezakhiwo eziveziwe ze-subendothelial.I-Platelet integrin kanye ne-GP complex ihlobene nezinqubo ezihlukahlukene zokuvuvukala futhi idlala indima ebalulekile ekwakhekeni kwe-platelet-leukocyte complex.Ngokuqondile, i-integrin aIIbb3 iyadingeka ukuze kwakhiwe inkimbinkimbi ezinzile ngokuhlanganisa i-fibrinogen ne-macrophage 1 antigen (Mac-1) receptor kuma-neutrophils.
Ama-platelet, ama-neutrophils namaseli e-vascular endothelial aveza ama-molecule athile okunamathela kwamaseli, abizwa ngokuthi i- selectin.Ngaphansi kwezimo zokuvuvukala, ama-platelet aveza i-P-selectin ne-neutrophil L-selectin.Ngemva kokusebenza kweplatelet, i-P-selectin ingase ibophe ku-ligand PSGL-1 ekhona kuma-neutrophils nama-monocyte.Ngaphezu kwalokho, ukubophezela kwe-PSGL-1 kuqala ukusabela kwesignali ye-intracellular cascade, okwenza ama-neutrophils asebenze nge-neutrophil integrin Mac-1 kanye ne-lymphocyte function-related antigen 1 (LFA-1).I-Mac-1 ecushiwe ibophezela ku-GPIb noma i-GPIIb/IIIa kuma-platelet nge-fibrinogen, ngaleyo ndlela kusimamise ukuxhumana phakathi kwama-neutrophils nama-platelet.Ngaphezu kwalokho, i-LFA-1 ecushiwe ingahlangana ne-platelet intercellular adhesion molecule 2 ukuze iqhubeke nokuzinzisa i-neutrophil-platelet complex ukukhuthaza ukunamathela kwesikhathi eside namaseli.
Ama-platelet nama-leukocyte adlala indima ebalulekile ekuphenduleni kwamasosha omzimba okuzalwa nokuguquguqukayo
Umzimba ungakwazi ukubona imizimba yangaphandle kanye nezicubu ezilimele ezifweni ezinzima noma ezingalapheki ukuze kuqalwe ukuphulukiswa kwesilonda kanye nendlela yokuvuvukala.Amasosha omzimba azalwa nawo futhi aguquguqukayo avikela umsingathi ekuthelelekeni, futhi amangqamuzana egazi amhlophe adlala indima ebalulekile ekwedluleleni phakathi kwalezi zinhlelo ezimbili.Ngokuqondile, ama-monocyte, ama-macrophage, ama-neutrophils namangqamuzana abulalayo emvelo adlala indima ebalulekile ohlelweni oluzalwa, kuyilapho ama-lymphocyte nama-subset awo adlala indima efanayo esimisweni sokuzivikela esiguquguqukayo.
Ukusebenzisana kwePlatelet kanye ne-leukocyte ekusebenzisaneni kwe-immune cell cell.I-Platelet isebenzisana nama-neutrophils nama-monocyte, futhi ekugcineni nge-M Φ Hlangana, lungisa futhi andise imisebenzi yabo yomphumela.Lokhu kusebenzisana kwe-platelet-leukocyte kuholela ekuvuvukeni ngokusebenzisa izindlela ezahlukene, kuhlanganise ne-NETosis.Izifinyezo: I-MPO: i-myeloperoxidase, i-ROS: izinhlobo ze-oksijini esebenzayo, TF: isici sethishu, NET: trap ye-neutrophil extracellular, NF- κ B: I-nuclear factor kappa B, M Φ: Ama-Macrophages.
Amasosha omzimba azalwa nawo
Indima yesimiso sokuzivikela ezifweni esizalwa nayo iwukuhlonza okungaqondile amagciwane ahlaselayo noma izingcezu zezicubu futhi kushukumise ukuvunyelwa kwazo.Uma izakhiwo ezithile zamangqamuzana ezibizwa ngokuthi ama-surface expression pattern recognition receptors (PRRs) zihlangana namaphethini amamolekyuli ahlobene ne-pathogen kanye namaphethini amamolekyuli ahlobene nomonakalo, amasosha omzimba azalwa nawo azosebenza.Kunezinhlobo eziningi zama-PRR, okuhlanganisa i-Toll-like receptor (TLR) kanye ne-RIG-1 efana nesamukeli (RLR).Lawa ma-receptors angenza kusebenze isici esiyinhloko sokuloba i-kappa B (NF- κ B) Iphinde ilawule izici eziningi zokuphendula komzimba okungaphakathi nokuguquguqukayo.Kuyathakazelisa ukuthi ama-platelet aphinde aveze izinhlobonhlobo zama-molecule e-immunoregulatory receptor ebusweni bawo kanye ne-cytoplasm, njenge-P-selectin, i-transmembrane protein CD40 ligand (CD40L), ama-cytokines (afana ne-IL-1 β, TGF- β） Kanye ne-TLR eqondene ne-platelet. Ngakho-ke, ama-platelet angasebenzisana namangqamuzana ahlukahlukene omzimba omzimba.
Ukusebenzisana kwe-Platelet-white cell ekuvikelekeni kwemvelo
Lapho ama-platelet engena noma ehlasela ukugeleza kwegazi noma izicubu, ama-platelet angelinye lamangqamuzana abona ukulimala kokuphela kwe-endothelial kanye namagciwane amagciwane kuqala.Ukuhlanganiswa kwe-platelet nokukhuthaza ukukhululwa kwama-agonists e-platelet ADP, i-thrombin ne-vWF, okuholela ekusebenzeni kwe-platelet kanye nokuvezwa kwe-platelet chemokine receptors C, CC, CXC kanye ne-CX3C, ngaleyo ndlela kubangele ama-platelet endaweni enegciwane noma ukulimala.
Isimiso somzimba sokuzivikela ezifweni sinqunywa kusengaphambili ngokofuzo ukuze sibone abahlaseli, njengamagciwane, amabhaktheriya, amagciwane kanye nobuthi, noma amanxeba ezicubu namanxeba.Iwuhlelo olungaqondile, ngoba noma iyiphi i-pathogen izokhonjwa njengeyangaphandle noma engeyona yona futhi itholakale ngokushesha.Amasosha omzimba azalwa nawo ancike kusethi yamaprotheni nama-phagocyte, abona izici ezigcinwe kahle ze-pathogen futhi enze kusebenze ngokushesha impendulo yokuzivikela komzimba ukusiza ukuqeda abahlaseli, noma ngabe umsingathi engakaze atholakale emagciwane athile ngaphambili.
Ama-neutrophils, ama-monocyte kanye namaseli e-dendritic angamangqamuzana omzimba azalwa nawo avamile egazini.Ukuqashwa kwabo kuyadingeka ukuze kutholakale impendulo eyanele yokuzivikela komzimba kusenesikhathi.Uma i-PRP isetshenziselwa imithi yokuvuselela, ukusebenzisana kwe-platelet-white cell kulawula ukuvuvukala, ukuphulukiswa kwesilonda nokulungiswa kwezicubu.I-TLR-4 kuma-platelet ivuselela ukusebenzisana kwe-platelet-neutrophil, elawula lokho okubizwa ngokuthi i-leukocyte oxidative ukuqhuma ngokulawula ukukhululwa kwezinhlobo ze-oxygen esebenzayo (ROS) kanye ne-myeloperoxidase (MPO) kuma-neutrophils.Ngaphezu kwalokho, ukusebenzisana phakathi kwe-platelet-neutrophil ne-neutrophil degranulation kuholela ekwakhekeni kwezicupho ze-neutrophil-extracellular (NETs).Ama-NET akhiwe yi-nucleus ye-neutrophil nokunye okuqukethwe kwe-neutrophil intracellular, okungabamba amagciwane futhi awabulale nge-NETosis.Ukwakhiwa kwama-NETs kuyindlela ebalulekile yokubulala yama-neutrophils.
Ngemuva kokusebenza kweplatelet, ama-monocyte angathuthela ezicutshini ezigulayo neziwohlokayo, lapho enza khona imisebenzi yokunamathela futhi akhiphe ama-molecule avuvukalayo angase aguqule izakhiwo ze-chemotaxis kanye ne-proteolytic.Ukwengeza, ama-platelet angenza i-monocyte i-NF- κ B isebenze ukuze ilawule ukusebenza kwe-effector yama-monocyte, okungumlamuleli oyinhloko wokuphendula okuvuvukala nokusebenza nokuhlukaniswa kwamangqamuzana omzimba omzimba.Ama-platelet aphinde akhuthaze ukuqhuma kwe-endogenous oxidative kwama-monocyte ukukhuthaza ukubhujiswa kwe-phagocytic pathogens.Ukukhululwa kwe-MPO kulamula ukuxhumana okuqondile phakathi kwe-CD40L-MAC-1 ye-platelet-monocyte.Ngokuthakazelisayo, lapho i-P-selectin ivuselela ama-platelet ngaphansi kwezimo zezicubu ezivuthayo ezibukhali nezingapheli, i-chemokines etholakala ku-platelet PF4, i-RANTES, i-IL-1 β kanye ne-CXCL-12 ingavimbela i-apoptosis ezenzakalelayo yama-monocyte, kodwa ikhuthaze ukuhlukaniswa kwawo kuma-macrophages.
I-Adaptive immune system
Ngemuva kokuthi isimiso somzimba sokuzivikela ezifweni esingaqondile sibona umonakalo we-microbial noma wezicubu, isimiso somzimba sokuzivikela ezimweni esiqondile sizothatha izintambo.Amasistimu aguquguqukayo ahlanganisa i-antigen-binding B lymphocyte (B cells) kanye nama-T lymphocyte avamile (Treg) ahlanganisa ukucaciswa kwamagciwane.Amaseli e-T angahlukaniswa cishe abe amaseli T asizayo (ama-Th cell) nama-cytotoxic T cell (ama-Tc cell, aziwa nangokuthi ama-T killer cell).Amaseli e-Th aphinde ahlukaniswe abe amaseli we-Th1, i-Th2 ne-Th17, anemisebenzi ebalulekile ekuvuvukeni.Amaseli angakwazi ukukhiqiza ama-cytokines ane-proinflammatory (isb. IFN- γ, TNF- β) Kanye nama-interleukin amaningana (isb, IL-17) Asebenza kahle kakhulu ekuvimbeleni igciwane le-intracellular kanye nokutheleleka kwamagciwane. Amaseli e-Tc angama-effector cells, angaqeda ama-microorganisms namaseli ahlosiwe angaphakathi kweseli namaseli.
Kuyathakazelisa ukuthi amaseli e-Th2 akhiqiza i-IL-4 futhi athinte i-M Φ Polarization, M Φ ukuvuselelwa okuqondiswayo M Φ 2 Phenotype, kuyilapho i-IFN- γ M Φ Ishintshela ekuvuvukeni kwe-M Φ 1 Phenotype, okuncike kumthamo kanye nesikhathi sama-cytokines.Ngemva kokuthi i-IL-4 isicushiwe, i-M Φ 2 yenza amaseli e-Treg ahlukanise abe amaseli e-Th2, bese ikhiqiza i-IL-4 eyengeziwe (i-loop yempendulo enhle).Amaseli e-T aguqula i-M Φ I-phenotype iqondiswe ku-phenotype yokuvuselela kabusha ngokuphendula ama-biological agents of tissue origin.Le nqubo isekelwe ebufakazini bokuthi ama-Th cell adlala indima ebalulekile ekulawuleni ukuvuvukala nokulungisa izicubu.
Ukusebenzisana kwe-Platelet-white cell ekugomeni okuguquguqukayo
Amasosha omzimba ashintshashintshayo asebenzisa ama-antigen-specific receptors futhi akhumbula amagciwane okuhlangatshezwane nawo ngaphambilini, futhi awabhubhise lapho ehlangana nomsingathi.Nokho, lezi zimpendulo zokuzivikela eziguquguqukayo zakhula kancane kancane.UKonias et al.Kubonisa ukuthi ingxenye yeplatelet inomthelela ekuboneni ingozi nokulungiswa kwezicubu, nokuthi ukusebenzisana phakathi kwamaplatelet nama-leukocyte kukhuthaza ukusebenza kokuphendula komzimba okuguquguqukayo.
Ngesikhathi sokuphendula komzimba okuguquguqukayo, ama-platelet akhuthaza izimpendulo ze-monocyte kanye ne-macrophage ngokusebenzisa i-DC ne-NK cell maturation, okuholela ekuphenduleni kwe-T cell ethile kanye ne-B cell.Ngakho-ke, izingxenye ze-platelet granule zithinta ngqo ukuzivikela okuguquguqukayo ngokuveza i-CD40L, i-molecule ebalulekile ekulawuleni ukusabela komzimba okuguquguqukayo.Ama-platelet nge-CD40L awagcini nje ngokudlala indima ekwethulweni kwe-antigen, kodwa aphinde athinte ukusabela kwe-T cell.Liu et al.Kwatholakala ukuthi ama-platelet alawula ukuphendula kwamaseli e-CD4 T ngendlela eyinkimbinkimbi.Lokhu kulawulwa okuhlukile kwama-CD4 T cell subsets kusho ukuthi ama-platelet akhuthaza amaseli e-CD4 T ukuthi aphendule ekuvuvukeni, ngaleyo ndlela akhiqize izimpendulo eziqinile eziphikisana nokuvuvukala nezilwa nokuvuvukala.
Ama-Platelets aphinde alawule ukusabela okuguquguqukayo kwamaseli e-B kuma-microbial pathogens.Kwaziwa kahle ukuthi i-CD40L kumaseli e-CD4 T acushiwe izocupha i-CD40 yamaseli B, inikeze isignali yesibili edingekayo ukuze kusebenze i-T-cell encike ku-B lymphocyte, ukuguqulwa kwe-allotype okulandelayo, kanye nokuhlukaniswa kwamaseli e-B nokwanda.Ngokuvamile, imiphumela ibonisa ngokucacile imisebenzi ehlukahlukene yamaplatelet ekugomeni okuguquguqukayo, okubonisa ukuthi ama-platelet axhuma ukusebenzisana phakathi kwamaseli e-T nama-B amaseli nge-CD40-CD40L, ngaleyo ndlela athuthukise impendulo ye-B cell encike ku-T.Ngaphezu kwalokho, ama-platelet acebile kuma-cell surface receptors, angakhuthaza ukusebenza kwe-platelet futhi akhulule inani elikhulu lama-molecule asebenzayo avuthayo kanye ne-biological agcinwe ezinhlayiyeni ezahlukene zeplatelet, ngaleyo ndlela athinte impendulo yokuzivikela engaphakathi neguquguqukayo.
Indima eyandisiwe ye-serotonin etholakala ku-platelet ku-PRP
I-Serotonin (i-5-hydroxytryptamine, i-5-HT) inendima ebalulekile ecacile ohlelweni lwezinzwa oluphakathi (CNS), kuhlanganise nokubekezelela ubuhlungu.Kulinganiselwa ukuthi iningi le-5-HT yomuntu likhiqizwa emgudwini wamathumbu bese kuthi ngokuhamba kwegazi, lapho limuncwa ama-platelet ngokusebenzisa i-serotonin reuptake transporter futhi igcinwe ezinhlayiyeni eziminyene ekugxilweni okuphezulu (65 mmol / L).I-5-HT iyi-neurotransmitter eyaziwayo kanye ne-hormone esiza ukulawula izinqubo ezihlukahlukene ze-neuropsychological ku-CNS (central 5-HT).Kodwa-ke, iningi le-5-HT likhona ngaphandle kwe-CNS (i-peripheral 5-HT), futhi ihileleke ekulawuleni imisebenzi yebhayoloji yesistimu kanye neselula yezinhlelo eziningi zezitho zomzimba, kuhlanganise nenhliziyo, amaphaphu, ama-gastrointestinal, urogenital kanye ne-platelet functional systems.I-5-HT ine-metabolism encike ekugxilweni kwezinhlobo ezihlukahlukene zamaseli, okuhlanganisa ama-adipocyte, amaseli e-epithelial namaseli amhlophe egazi.I-Peripheral 5-HT iphinde ibe yi-immune modulator enamandla, engashukumisa noma ivimbele ukuvuvukala futhi ithinte amangqamuzana omzimba ahlukahlukene ngokusebenzisa i-5-HT receptor (5HTR) yayo ethile.
I-Paracrine kanye ne-autocrine mechanism ye-HT
Umsebenzi we-5-HT ulamula ukusebenzisana kwawo nama-5HTR, okuwumndeni omkhulu onamalungu ayisikhombisa (5-HT 1 - 7) kanye nama-subtypes okungenani angu-14 ahlukene, okuhlanganisa nelungu elisanda kutholwa i-5-HT 7, i-peripheral kanye umsebenzi ekulawuleni ubuhlungu.Enqubweni ye-platelet degranulation, ama-platelet acushiwe afihla inombolo enkulu ye-platelet-derived 5-HT, engakhuthaza ukufinyela kwe-vascular futhi ikhuthaze ukusebenza kwama-platelet aseduze nama-lymphocyte ngokusebenzisa inkulumo ye-5-HTR kumaseli e-endothelial, amaseli emisipha abushelelezi kanye amangqamuzana omzimba.Pacala et al.Umphumela we-mitotic we-5-HT kumaseli e-vascular endothelial wacwaningwa, futhi amandla okukhuthaza ukukhula kwemithambo yegazi eyonakele ngokuvuselela i-angiogenesis yanqunywa.Ukuthi lezi zinqubo zilawulwa kanjani akucaci ngokuphelele, kodwa kungase kuhlanganise umehluko wezindlela zesignali ezimbili ku-microcircuit yezicubu ukuze ulawule imisebenzi yamangqamuzana e-vascular endothelial kanye namaseli emisipha abushelelezi, ama-fibroblasts namaseli omzimba ngokusebenzisa ama-receptors athile e-5-HT kulawa maseli. .Umsebenzi we-autocrine weplatelet 5-HT ngemva kokwenziwa kusebenze kweplatelet uye wachazwa [REF].Ukukhishwa kwe-5-HT kuthuthukisa ukusebenza kwama-platelet kanye nokuqashwa kwamaplatelet ajikelezayo, okuholela ekusebenziseni ukusabela kwe-signal cascade kanye nama-effectives akhuphukayo asekela ukusebenza kabusha kwe-platelet.
Umphumela we-Immunomodulatory 5-HT
Ubufakazi obuningi bubonisa ukuthi i-serotonin ingadlala indima ku-5HTR ehlukile njengemoduli yomzimba.Ngokusho kwe-5HTR evezwe kuma-leukocyte ahlukahlukene ahilelekile ekuphenduleni kokuvuvukala, i-5-HT etholakala ku-platelet isebenza njengesilawuli sokuzivikela somzimba kokubili amasosha omzimba azalwa futhi aguquguqukayo.I-5-HT ingashukumisa ukwanda kwe-Treg futhi ilawule imisebenzi yamaseli B, amangqamuzana abulalayo emvelo nama-neutrophils ngokuqasha i-DC nama-monocyte kusayithi lokuvuvukala.Ucwaningo lwakamuva lubonise ukuthi i-platelet-derived 5-HT ingalawula umsebenzi wamaseli omzimba ngaphansi kwezimo ezithile.Ngakho-ke, usebenzisa i-C-PRP, ukuhlushwa kwe-platelet kukhulu kune-1 × 10 6 / µ L kungasiza kakhulu ukuthutha ukuhlushwa kwe-5-HT etholakala kumaplatelet amakhulu kuya kwezicubu.Ku-microenvironment ebonakala ngezingxenye ezivuthayo, i-PRP ingasebenzisana namaseli amaningana omzimba adlala indima ebalulekile kulawa ma-pathologies, angase athinte imiphumela yomtholampilo.
Umfanekiso obonisa impendulo ye-5-HT eminingi ngemva kokusebenza kwamaplatelet e-PRP avuthayo.Ngemuva kokusebenza kwama-platelet, ama-platelet akhulula ama-granules awo, kufaka phakathi i-5-HT kuma-granules aminyene, anemiphumela eminingi ehlukile kumaseli ahlukahlukene omzimba, amaseli e-endothelial namaseli emisipha abushelelezi.Izifinyezo: I-SMC: amaseli emisipha abushelelezi, i-EC: amaseli e-endothelial, i-Treg: i-T lymphocyte evamile, i-M Φ: ama-Macrophages, i-DC: amaseli e-dendritic, i-IL: i-interleukin, i-IFN- γ: I-Interferon γ。 Iguquliwe futhi yashintshwa kusukela ku-Everts et al.kanye noHull et al.
Umphumela we-analgesic we-PRP
Ama-platelet acushiwe azokhulula abaxhumanisi abaningi be-pro-inflammatory and anti-inflammatory, abangeke babangele ubuhlungu kuphela, kodwa futhi banciphise ukuvuvukala nobuhlungu.Uma sekusetshenziswe, i-PRP ejwayelekile ye-platelet dynamics ishintsha i-microenvironment ngaphambi kokulungiswa kwezicubu nokuvuselelwa ngokusebenzisa izindlela ezihlukahlukene eziyinkimbinkimbi ezihlobene ne-anabolism kanye ne-catabolism, ukwanda kwamaseli, ukuhlukaniswa kanye nokulawulwa kwe-stem cell.Lezi zici ze-PRP ziholela ekusetshenzisweni kwe-PRP ezimweni ezihlukahlukene ze-pathological zomtholampilo ngokuvamile ezihlotshaniswa nobuhlungu obungapheli (njengokulimala kwezemidlalo, isifo samathambo, isifo somgogodla kanye nesilonda esingapheli esiyinkimbinkimbi), nakuba indlela eqondile ingakanqunywa ngokugcwele.
Ngo-2008, u-Evertz et al.Kuyisivivinyo sokuqala esilawulwa ngokungahleliwe ukubika umphumela we-analgesic wokulungiselela i-PRP, olungiselelwa kusukela kungqimba olunsundu lwezinga le-autologous erythrocyte sedimentation futhi lwenziwe lusebenze nge-autologous thrombin ngemva kokuhlinzwa kwehlombe.Baphawule ukwehla okuphawulekayo kwezilinganiso zesilinganiso se-analogue esibukwayo, ukusetshenziswa kwama-analgesics asekelwe ku-opioid, nokuvuselelwa okuyimpumelelo kwangemva kokuhlinzwa.Kuyaphawuleka ukuthi abonisa umphumela we-analgesic wamaplatelet acushiwe futhi acabange ngomshini wamaplatelet akhipha i-5-HT.Ngamafuphi, ama-platelet alele ku-PRP esanda kulungiswa.Ngemuva kokusebenza kwamaplatelet ngokuqondile noma ngokungaqondile (isici sezicubu), ama-platelet ashintsha ukuma futhi akhiqize amanga ngokwanele ukuze akhuthaze ukuhlangana kweplatelet.Bese, bakhipha izinhlayiya ze-intracellular α- Futhi eziminyene.Izicubu eziphathwe nge-PRP ecushiwe zizohlaselwa yi-PGF, ama-cytokines namanye ama-lysosomes eplatelet.Ngokuqondile, lapho izinhlayiya eziminyene zikhulula okuqukethwe kwazo, zizokhipha inani elikhulu le-5-HT elilawula ubuhlungu.Ku-C-PRP, ukuhlushwa kwe-platelet kuphindwe izikhathi ezingu-5 kuya kwezingu-7 kunegazi le-peripheral.Ngakho-ke, ukukhululwa kwe-5-HT kuma-platelet kuyisayensi yezinkanyezi.Kuyathakazelisa ukuthi uSprott et al.Umbiko waphawula ukuthi ubuhlungu buye bakhululeka kakhulu ngemva kwe-acupuncture kanye ne-moxibustion, ukuhlushwa kweplatelet etholakala ku-5-HT kwancishiswa kakhulu, bese izinga le-plasma le-5-HT lenyuka.
Ku-peripheral, platelets, mast cells namaseli e-endothelial azokhulula i-5-HT engapheli ngesikhathi sokulimala kwezicubu noma ukuhlukumezeka kokuhlinzwa.Kuyathakazelisa ukuthi izinhlobonhlobo ze-5-HT zokwamukela ama-neurons zitholwe endaweni ye-peripheral, okuqinisekisile ukuthi i-5-HT ingaphazamisa ukudluliselwa kwe-nociceptive endaweni ye-peripheral.Lezi zifundo zibonisa ukuthi i-5-HT ingathinta ukudluliswa kwe-nociceptive kwezicubu ze-peripheral ngokusebenzisa i-5-HT1, 5-HT2, 5-HT3, 5-HT4 kanye ne-5-HT7 receptors.
Isistimu ye-5-HT imele uhlelo olunamandla olunganciphisa futhi lwandise izinga lobuhlungu ngemva kokuvuselela okuyingozi.Ukulawulwa kwe-central and peripheral of signals nociceptive kanye nezinguquko ohlelweni lwe-5-HT kuye kwabikwa ezigulini ezinezinhlungu ezingapheli.Eminyakeni yamuva nje, inani elikhulu lezifundo ligxile endimeni ye-5-HT kanye nama-receptors ayo ekucubunguleni nasekulawuleni ulwazi oluyingozi, okuholela emithini efana ne-serotonin reuptake inhibitors (SSRI) ekhethiwe.Lesi sidakamizwa sivimbela ukutholwa kabusha kwe-serotonin kuma-presynaptic neurons ngemva kokukhululwa kwe-serotonin.Kuthinta ubude nokuqina kokuxhumana kwe-serotonin futhi kungenye indlela yokwelapha ubuhlungu obungapheli.Ucwaningo olwengeziwe lomtholampilo luyadingeka ukuze uqonde ngokucacile indlela yamangqamuzana ye-PRP-derived 5-HT yokulawulwa kobuhlungu ezifweni ezingapheli neziwohlokayo.
Enye idatha yokuxazulula umphumela we-analgesic ongaba khona we-PRP ingatholakala ngemva kokuhlolwa kwemodeli yezilwane ezidabukisayo.Iziphetho zezibalo eziqhathanisayo kulawa mamodeli ziyinselele ngoba lezi zifundo ziqukethe okuguquguqukayo okuningi kakhulu.Noma kunjalo, ezinye izifundo zomtholampilo ziye zabhekana nemiphumela ye-nociceptive ne-analgesic ye-PRP.Ucwaningo oluningana lubonise ukuthi iziguli ezithola ukwelashwa kwe-tendinosis noma izinyembezi ze-rotator cuff zinezinhlungu ezincane.Ngokuphambene nalokho, ezinye izifundo eziningana zibonise ukuthi i-PRP inganciphisa noma iqede ngisho nobuhlungu beziguli ezine-tendon degeneration, i-OA, i-plantar fasciitis nezinye izifo zezinyawo nezinyawo.Ukugxila kokugcina kweplatelet kanye nokwakheka kwamaseli ezinto eziphilayo kuye kwabonakala njengezici ezibalulekile ze-PRP, okusiza ukugcina umphumela we-analgesic ongaguquki ngemva kokusetshenziswa kwe-PRP.Okunye okuguquguqukayo kuhlanganisa indlela yokulethwa kwe-PRP, ubuchwepheshe bohlelo lokusebenza, i-platelet activation protocol, izinga lomsebenzi we-biological we-PGF nama-cytokines akhishwe, uhlobo lwezicubu zohlelo lokusebenza lwe-PRP kanye nohlobo lokulimala.
Kuyaphawuleka ukuthi i-Kuffler ixazulule amandla e-PRP ekunciphiseni ubuhlungu ezigulini ezinobuhlungu obuncane be-neuropathic obungapheli, okwesibili ku-nerve eyonakele engavuseleli.Inhloso yalolu cwaningo ukuphenya ukuthi ubuhlungu be-neuropathic bungancishiswa noma buncishiswe ngenxa ye-PRP ekhuthaza ukuvuselelwa kwe-axonal kanye ne-target nerve reinnervation.Ngokumangalisayo, phakathi kweziguli ezithola ukwelashwa, ubuhlungu be-neuropathic busaqedwa noma buncishisiwe okungenani eminyakeni eyisithupha ngemva kokuhlinzwa.Ngaphezu kwalokho, zonke iziguli zaqala ukukhulula ubuhlungu phakathi namasonto amathathu ngemva kokusetshenziswa kwe-PRP.
Muva nje, imiphumela efanayo ye-PRP ye-analgesic iye yabonwa emkhakheni wesilonda sangemva kokuhlinzwa nokunakekelwa kwesikhumba.Kuyathakazelisa ukuthi abalobi babike izici zomzimba zobuhlungu besilonda ezihambisana nokulimala kwe-vascular kanye ne-skin tissue hypoxia.Baphinde baxoxa ngokubaluleka kwe-angiogenesis ekwenzeni ngcono umoya-mpilo kanye nokulethwa kwezakhi.Ucwaningo lwabo lubonise ukuthi uma kuqhathaniswa neqembu lokulawula, iziguli ezithola ukwelashwa kwe-PRP zazinobuhlungu obuncane futhi zanda kakhulu i-angiogenesis.Ekugcineni, uJoal nozakwabo benza ukubuyekezwa okuhlelekile nokuhlaziywa kwe-meta futhi baphetha ngokuthi i-PRP inganciphisa ubuhlungu ngemva kokusebenzisa i-PRP ezinkomba zamathambo, ikakhulukazi ezigulini ezithola i-epicondylitis yangaphandle kanye nokwelashwa kwe-knee OA.Ngeshwa, lolu cwaningo aluzange lucacise imiphumela yamangqamuzana egazi amhlophe, ukuhlushwa kwe-platelet noma ukusetshenziswa kwama-activator e-platelet exogenous, ngoba lezi ziguquguqukayo zizothinta ukusebenza kahle okuphelele kwe-PRP.Ukugxiliswa kweplatelet ye-PRP efanelekile yokunciphisa ubuhlungu obukhulu akucaci.Kumodeli wegundane we-tendinosis, ukuhlushwa kweplatelet kwakuyi-1.0 × 10 6 / μ Ku-L, ubuhlungu bungakhululeka ngokuphelele, kuyilapho ukukhululeka kobuhlungu okubangelwa i-PRP ngesigamu sokuhlushwa kweplatelet kuncipha kakhulu.Ngakho-ke, sikhuthaza izifundo eziningi zomtholampilo ukuze ziphenye imiphumela ye-analgesic yamalungiselelo ahlukene e-PRP.
I-PRP kanye nomphumela we-angiogenesis
Amalungiselelo e-C-PRP emithini yokuvuselela kabusha enembile avumela ukulethwa kwama-biomolecules akhishwe ukugxila okuphezulu kwamaplatelet acushwe ezindaweni ezihlosiwe zezicubu.Ngakho-ke, kuye kwaqaliswa ukusabela okuhlukahlukene kwe-cascade, okufaka isandla ekulawulweni kwamasosha omzimba esizeni, inqubo yokuvuvukala kanye ne-angiogenesis ukukhuthaza ukuphulukiswa nokulungiswa kwezicubu.
I-Angiogenesis yinqubo enezinyathelo eziningi enamandla ehlanganisa ukuhluma kanye nama-microvessels ezicubu asuka emithanjeni yegazi evele ikhona.I-Angiogenesis ithuthuke ngenxa yezinqubo ezihlukahlukene zezinto eziphilayo, okuhlanganisa ukufuduka kwamangqamuzana e-endothelial, ukwanda, ukuhlukaniswa nokuhlukana.Lezi zinqubo zamangqamuzana ziyizimfuneko zokwakheka kwemithambo yegazi emisha.Zibalulekile ekukhuleni kwemithambo yegazi ekhona ngaphambili ukuze kubuyiselwe ukugeleza kwegazi nokusekela umsebenzi ophezulu we-metabolic wokulungiswa kwezicubu nokuvuselelwa kwezicubu.Le mithambo yegazi emisha ivumela ukulethwa komoyampilo nezakhamzimba, kanye nokususwa kwemikhiqizo evela ezicutshini ezilashiwe.
Umsebenzi we-angiogenesis ulawulwa yi-angiogenic factor VEGF evuselelayo kanye nezici ezilwa ne-angiogenic (isb., i-angiostatin ne-thrombospondin-1 [TSP-1]).Ku-microenvironment egulayo necekeleke phansi (okuhlanganisa ukungezwani komoyampilo okuphansi, i-pH ephansi nezinga eliphezulu le-lactic acid), izici zendawo ze-angiogenic zizobuyisela umsebenzi we-angiogenesis.
Imidiya eminingana encibilikayo yeplatelet, njenge-FGF eyisisekelo ne-TGF- β Futhi i-VEGF ingashukumisa amangqamuzana e-endothelial ukukhiqiza imithambo yegazi emisha.I-Landsdown ne-Fortier ibike imiphumela ehlukahlukene ehlobene nokwakheka kwe-PRP, okuhlanganisa nemithombo ye-intraplatelet yezilawuli eziningi ze-angiogenic.Ngaphezu kwalokho, baphetha ngokuthi ukwanda kwe-angiogenesis kunomthelela ekwelapheni kwesifo se-MSK ezindaweni ezine-vascularization empofu, njenge-meniscus izinyembezi, ukulimala kwe-tendon nezinye izindawo ezine-vascularization embi.
Ukukhuthaza kanye nezakhiwo ze-anti-angiogenic platelet
Emashumini ambalwa eminyaka adlule, izifundo ezishicilelwe ziye zafakazela ukuthi ama-platelet adlala indima ebalulekile ku-hemostasis eyinhloko, ukwakheka kwamahlule, ukukhula kwesici kanye nokukhululwa kwe-cytokine, nokulawulwa kwe-angiogenesis njengengxenye yenqubo yokulungisa izicubu.Okuxakayo ukuthi, i-PRP α- Ama-granules aqukethe i-arsenal yezinto ezikhulayo ze-pro-angiogenic, amaprotheni e-anti-angiogenic nama-cytokines (afana ne-PF4, i-plasminogen activator inhibitor-1 ne-TSP-1), futhi aqondise ukukhululwa kwezici ezithile ezidlala indima. .Indima ku-angiogenesis.Ngakho-ke, indima ye-PRP ekulawuleni ukulawulwa kwe-angiogenesis ingase ichazwe ngokusebenza kwe-cell cell cell receptors, i-TGF- β Qalisa ukusabela kwe-pro-angiogenic kanye ne-anti-angiogenic.Ikhono lama-platelet ukusebenzisa indlela ye-angiogenesis liqinisekisiwe ku-angiogenesis ye-pathological kanye ne-tumor angiogenesis.
Isici sokukhula se-angiogenic esivela ku-platelet kanye nesici sokukhula esilwa ne-angiogenic, siphuma ku-α- Futhi ama-molecule aminyene nanamathelayo.Okubaluleke kakhulu, ngokuvamile kuyamukelwa ukuthi umphumela ophelele wamaplatelet ku-angiogenesis u-pro-angiogenic futhi uyavuselela.Kulindeleke ukuthi ukwelashwa kwe-PRP kuzolawula ukungeniswa kwe-angiogenesis, okuzofaka isandla emthelela wokwelapha wezifo eziningi, njengokuphulukiswa kwesilonda nokulungiswa kwezicubu.Ukuphathwa kwe-PRP, ikakhulukazi ukuphathwa kwe-PGF ephezulu yokuhlushwa kanye namanye ama-cytokines e-platelet, kungabangela i-angiogenesis, i-angiogenesis kanye ne-arteriogenesis, ngoba i-stromal cell-derived factor 1a ibophezela ku-CXCR4 receptor kumaseli e-endothelial progenitor.UBill et al.Kuphakanyiswa ukuthi i-PRP ikhulise i-ischemic neovascularization, okungenzeka kube ngenxa yokukhuthazwa kwe-angiogenesis, i-angiogenesis ne-arteriogenesis.Kumodeli yabo ye-in vitro, ukwanda kwamangqamuzana e-endothelial kanye nokwakheka kwe-capillary kudalwe inani elikhulu lama-PDG ahlukene, lapho i-VEGF eyayiyisikhuthazi esiyinhloko se-angiogenic.Esinye isici esibalulekile nesibalulekile sokubuyisela indlela ye-angiogenesis ukusebenzisana phakathi kwama-PGF amaningi.Richardson et al.Kwafakazelwa ukuthi umsebenzi we-synergistic we-angiogenic factor platelet-derived growth factor-bb (PDGF-BB) kanye ne-VEGF yaholela ekwakhekeni okusheshayo kwenethiwekhi ye-vascular evuthiwe uma kuqhathaniswa nomsebenzi wesici sokukhula somuntu ngamunye.Umthelela ohlangene walezi zici usanda kuqinisekiswa ocwaningweni lokuthuthukisa ukujikeleza kokuqina kobuchopho kumagundane ane-hypoperfusion yesikhathi eside.
Okubaluleke kakhulu, ucwaningo lwe-in vitro lwakala umphumela okhulayo wamaseli endothelial we-umbilical vein endothelial kanye nokugxila kwe-platelet ehlukahlukene ekukhethweni kwedivayisi yokulungiswa kwe-PRP kanye nesu lomthamo we-platelet, futhi imiphumela yabonisa ukuthi umthamo ophelele we-platelet wawuyi-1.5 × 10 6 platelet/ μ 50. Ukukhuthaza i-angiogenesis.Ukugcwala kweplatelet ephezulu kakhulu kungase kuvimbele inqubo ye-angiogenesis, ngakho-ke umphumela uba mubi.
Ukuguga kwamaseli, ukuguga kanye ne-PRP
I-cell senescence ingadalwa yizisusa ezihlukahlukene.Lena inqubo lapho amangqamuzana ayeka ukuhlukana futhi enze izinguquko eziyingqayizivele ze-phenotypic ukuze avimbele ukukhula okungavinjelwe kwamangqamuzana awonakele, okudlala indima ebalulekile ekuvimbeleni umdlavuza.Enqubweni yokuguga ngokomzimba, ukuguga kokuphindaphinda kwamaseli kuzophinde kukhuthaze ukuguga kwamangqamuzana, kanye nekhono lokuvuselela ama-MSC lizoncishiswa.
Imiphumela yokuguga nokuguga kwamaseli
Ku-vivo, izinhlobo eziningi zamaseli zizoguga futhi ziqoqwe ezicutshini ezihlukahlukene ngesikhathi sokuguga, phakathi kwazo kunenani elikhulu lamaseli aguga.Ukuqoqwa kwamangqamuzana asebekhulile kubonakala kukhula ngokwanda kweminyaka, ukulimala kwamasosha omzimba, ukulimala kwezicubu noma izici ezihlobene nokucindezeleka.Indlela yokuguga kwamaselula iye yabonakala njengesici se-pathogenic yezifo ezihlobene nobudala, njenge-osteoarthritis, i-osteoporosis kanye ne-intervertebral disc degeneration.Izinhlobonhlobo zezisusa zizokhulisa ukuguga kwamangqamuzana.Ekuphenduleni, i-senescence-related secretory phenotype (SASP) izokhipha ukugxila okuphezulu kwamaseli amaprotheni nama-cytokines.Le phenotype ekhethekile ihlobene namaseli asebekhulile, lapho akhiqiza khona amazinga aphezulu ama-cytokines avuthayo (njenge-IL-1, IL-6, IL-8), izici zokukhula (njenge-TGF- β, HGF, VEGF, PDGF), I-MMP, ne-cathepsin.Uma kuqhathaniswa nabantu abasha, i-SAPS ibonakale ikhula ngokukhula, ngenxa yokuthi inqubo yesimo esiqhubekayo iyashabalala, okuholela ekugugeni kwamaseli kanye nokuncipha kwamandla okuvuselela.Ngokuqondile, ezifweni ezihlangene kanye nezifo zemisipha yamathambo.Mayelana nalokhu, ukuguga kwamasosha omzimba kubhekwa njengoshintsho oluphawulekayo ekuthunjweni kwamangqamuzana omzimba omzimba, okubonisa ukuthi ukuhlushwa kwe-TNF-a, IL-6 kanye / noma i-Il-1b kwanda, okuholela ekuvuvukeni okungapheli okuphansi.Kuyaphawuleka ukuthi ukungasebenzi kahle kwe-stem cell kuhlobene nezinqubo ezizimele ezingezona amaselula, njengamaseli aguga, ikakhulukazi ukukhiqizwa kwezinto ezikhuthaza ukuvuvukala nezilwa nokuvuselela nge-SASP.
Ngokuphambene nalokho, i-SASP ingaphinde igqugquzele ipulasitiki yamaseli kanye nokuhlelwa kabusha kwamaseli aseduze.Ngaphezu kwalokho, i-SASP ingahlela ukuxhumana nabaxhumanisi abahlukahlukene bamasosha omzimba futhi isebenze amaseli omzimba ukuze akhuthaze ukucaciswa kwamaseli aguga.Ukuqonda indima kanye nomsebenzi wamangqamuzana asebekhulile kuzofaka isandla ekwelapheni nasekulungisweni kabusha kwezicubu zemisipha ye-MSK namanxeba angapheli.
Kuyaphawuleka ukuthi uRitcka et al.Ucwaningo olunzulu lwenziwa, futhi indima eyinhloko nenenzuzo ye-SASP ekukhuthazeni ipulasitiki yamangqamuzana nokuvuselelwa kwezicubu kwatholakala, futhi kwasungulwa nomqondo wokulethwa kokwelashwa kwesikhashana kwamangqamuzana asebekhulile.Basho ngokuqapha ukuthi ukuguga ngokuyinhloko kuyinqubo enenzuzo nevuselelayo.
Ukuguga kwamaseli namandla e-PRP
Njengoba inani lama-stem cell liyancipha, ukuguga kuzothinta ukusebenza kwamaseli e-stem.Ngokufanayo, kubantu, izici ze-stem cell (njengokoma, ukwanda nokuhlukaniswa) nazo ziyancipha ngokuya ngeminyaka.U-Wang no-Nirmala babike ukuthi ukuguga kuzonciphisa izici ze-tendon cell stem cell kanye nenani lama-receptor factor.Ucwaningo lwezilwane lubonise ukuthi ukugxila kwe-PDGF emahhashi amancane kwakuphezulu.Baphetha ngokuthi ukwanda kwenani lama-GF receptors kanye nenani le-GF kubantu abasha kungase kube nokusabela okungcono kwamaselula ekwelashweni kwe-PRP kunabantu abadala kubantu abasha.Lokhu okutholakele kuveza ukuthi kungani ukwelashwa kwe-PRP kungase kungasebenzi kahle noma kungasebenzi ezigulini esezikhulile ezinamaseli ambalwa kanye “nekhwalithi embi”.Kuye kwafakazelwa ukuthi inqubo yokuguga ye-cartilage yokuguga iguqulwa futhi isikhathi sokuphumula sama-chondrocyte sanda ngemva kokujova kwe-PRP.Jia et al.Isetshenziselwa ukutadisha i-mouse dermal fibroblasts in vitro photoaging, ngokwelashwa kwe-PRP nangaphandle kwayo, ukuze kucaciswe indlela yokuphikisa kwe-PGF kule modeli.Iqembu le-PRP libonise umphumela oqondile kumatrix we-extracellular, ukwanda kohlobo lwe-collagen I-collagen nokunciphisa ukuhlanganiswa kwe-metalloproteinase, okubonisa ukuthi i-PRP ingamelana nokuguga kwamaseli, kanye nesifo se-MSK esiwohlokayo.
Kwesinye isifundo, i-PRP yasetshenziselwa ukuqoqa amaseli e-stem amathambo asebekhulile kumagundane asebekhulile.Kunqunywe ukuthi i-PRP ingakwazi ukubuyisela imisebenzi ehlukahlukene ye-stem cell kusukela ekugugeni, njengokwanda kwamaseli kanye nokwakhiwa kwekholoni, futhi yakhe kabusha izimpawu ezihlobene nokuguga kwamaseli.
Muva nje, u-Oberlohr kanye nozakwabo bafunde kabanzi indima yokuguga kwamangqamuzana ekwenzeni buthakathaka ukuvuselelwa kwemisipha, futhi bahlola i-PRP kanye ne-platelet-poor plasma (PPP) njengezinketho zokwelapha eziphilayo zokulungisa imisipha yamathambo.Babenombono wokuthi ukwelashwa kwe-PRP noma i-PPP yokulungisa imisipha yohlaka kuzosekelwe ezintweni zebhayoloji ezenzelwe omaka beselula abathile be-SASP nezinye izici eziholela ekuthuthukisweni kwe-fibrosis.
Kunengqondo ukukholelwa ukuthi ngaphambi kokusetshenziswa kwe-PRP, ukuguga kwamaseli okuhlosiwe kungathuthukisa izici zokuvuselela ukusebenza kokwelashwa kwebhayoloji ngokunciphisa izici ze-SASP zendawo.Kuye kwaphakanyiswa ukuthi enye inketho yokuthuthukisa imiphumela ye-PRP kanye nokwelashwa kwe-PPP yokuvuselelwa kwemisipha yamathambo ukukhipha ngokukhetha amangqamuzana asebekhulile nama-scavengers aguga.Akungabazeki ukuthi imiphumela yocwaningo lwakamuva ngomphumela we-PRP ekugugeni kwamaseli nokuguga iyathakazelisa, kodwa isesigabeni sokuqala.Ngakho-ke, akunangqondo ukwenza noma yiziphi iziphakamiso ngalesi sikhathi.
(Okuqukethwe yile ndatshana kuphrintwe kabusha, futhi asinikezeli nganoma yisiphi isiqinisekiso esicacile noma esishiwoyo sokunemba, ukwethembeka noma ukuphelela kokuqukethwe okuqukethwe kulesi sihloko, futhi asinasibopho ngemibono yalesi sihloko, sicela uqonde.)
Isikhathi sokuthumela: Mar-01-2023