Namuhla, umqondo owaziwa ngokuthi i-PRP uqale ukuvela emkhakheni we-hematology ngawo-1970.Izazi ze-Hematologists zakha igama elithi PRP emashumini eminyaka adlule ukuchaza i-plasma etholakala ekubaleni kwe-platelet ephakeme kunenani eliyisisekelo legazi le-peripheral.Eminyakeni engaphezu kweshumi kamuva, i-PRP yasetshenziswa ekuhlinzweni kwe-maxillofacial njengendlela ye-platelet rich fibrin (PRF).Okuqukethwe kwe-fibrin kulokhu okuphuma ku-PRP kunenani elibalulekile ngenxa yokunamathela kwayo nezici eziqinile, kuyilapho i-PRP inezindawo eziphikisana nokuvuvukala futhi ivuselela ukwanda kwamaseli.Ekugcineni, ngawo-1990, i-PRP yaqala ukuduma.Ekugcineni, lobu buchwepheshe badluliselwa kweminye imikhakha yezokwelapha.Kusukela ngaleso sikhathi, lolu hlobo lwe-biology enhle luye lwafundwa kabanzi futhi lusetshenziswa ekwelapheni ukulimala okuhlukahlukene kwe-musculoskeletal yabasubathi abaqeqeshiwe, okuqhubekisela phambili ukunakwa kwayo kabanzi kwabezindaba.Ngaphandle kokuphumelela kwemithi yamathambo nezemidlalo, i-PRP iphinde isetshenziswe ku-ophthalmology, gynecology, urology kanye ne-cardiology, izingane kanye nokuhlinzwa kwepulasitiki.Eminyakeni yamuva nje, i-PRP iphinde yadunyiswa yi-dermatologists ngokukwazi kwayo ekwelapheni izilonda zesikhumba, ukulungiswa kwezibazi, ukuvuselelwa kwezicubu, ukuvuselela isikhumba ngisho nokulahlekelwa izinwele.
Uma ucabangela iqiniso lokuthi i-PRP ingakwazi ukuphatha ngokuqondile izinqubo zokuphulukisa nokuvuvukala, kuyadingeka ukwethula i-cascade yokuphulukisa njengereferensi.Inqubo yokuphulukisa ihlukaniswe ngezigaba ezine ezilandelayo: i-hemostasis;Ukuvuvukala;Ukwanda kweseli kanye ne-matrix, futhi ekugcineni ukulungiswa kabusha kwesilonda.
Ukuphulukiswa Kwezicubu
I-tissue heals cascade reaction icushiwe, okuholela ekuhlanganisweni kweplatelet Ukwakheka kwamahlule kanye nokuthuthukiswa kwe-matrix ye-extracellular yesikhashana (ECM).Ngemuva kwalokho, ama-platelet anamathela kuphrotheni eveziwe ye-collagen ne-ECM, okubangela ukukhululwa kwama-molecule e-bioactive akhona kuma-granules.Ama-platelet aqukethe izinhlobonhlobo zamangqamuzana e-bioactive, okuhlanganisa izici zokukhula, izici ze-chemotherapy nama-cytokines, kanye nabalamuli be-proinflammatory, njenge-prostaglandin, i-prostate cyclin, i-histamine, i-thromboxane, i-serotonin ne-bradykinin.
Isigaba sokugcina senqubo yokuphola sincike ekulungisweni kabusha kwesilonda.Ukulungiswa kabusha kwezicubu kulawulwa ngokuqinile ukuze kusungulwe ibhalansi phakathi kwe-anabolic kanye nokusabela kwe-catabolic.Kulesi sigaba, i-platelet-derived growth factor (PDGF) kanye ne-transforming growth factor (TGF- β) i-Fibronectin ne-fibronectin ikhuthaza ukwanda nokufuduka kwe-fibroblasts, kanye nokuhlanganiswa kwezingxenye ze-ECM.Nokho, isikhathi sokuvuthwa kwesilonda sincike kakhulu ebukhulu besilonda, izici zomuntu ngamunye kanye nekhono elithile lokuphulukisa lezicubu ezilimele.Ezinye izici ze-pathophysiological kanye ne-metabolic zingathinta inqubo yokuphulukisa, njengezicubu ze-ischemia, i-hypoxia, ukutheleleka, ukungalingani kwesici sokukhula, kanye nezifo ezihlobene ne-metabolic syndrome.
I-proinflammatory microenvironment iphazamisa inqubo yokuphulukisa.Okuyinkimbinkimbi kakhulu ukuthi umsebenzi ophezulu we-protease uvimbela isenzo semvelo se-growth factor (GF).Ngaphezu kwezakhiwo zayo ze-mitotic, angiogenic kanye ne-chemotactic, i-PRP iphinde ibe umthombo ocebile wezici eziningi zokukhula.Lawa ma-biomolecules angase alwe nemiphumela eyingozi ezicutshini ezivuvukalayo ngokulawula ukwanda kokuvuvukala nokusungula izisusa ze-anabolic.Ngokucabangela lezi zici, abacwaningi bangathola amandla amakhulu ekwelapheni ukulimala okuhlukahlukene okuyinkimbinkimbi.
Izifo eziningi, ikakhulukazi lezo zemvelo ye-musculoskeletal, zincike kakhulu emikhiqizweni yezinto eziphilayo ezilawula inqubo yokuvuvukala, njenge-PRP yokwelapha i-osteoarthritis.Kulokhu, impilo ye-articular cartilage incike ebhalansini eqondile ye-anabolic kanye nokusabela kwe-catabolic.Unalesi simiso engqondweni, ukusetshenziswa kwama-agent athile ebhayoloji angaphumelela ekuzuzeni ukulinganisela okunempilo.I-PRP ngoba ikhipha ama-platelet α- Izici zokukhula eziqukethwe kuma-granules zisetshenziselwa kakhulu ukulawula amandla okuguqulwa kwezicubu, okunciphisa nobuhlungu.Eqinisweni, enye yezinhloso eziyinhloko zokwelashwa kwe-PRP ukumisa i-microenvironment eyinhloko yokuvuvukala kanye ne-catabolic futhi ikhuthaze ukuguqulwa kwezidakamizwa ezilwa nokuvuvukala.Abanye ababhali baye babonisa ngaphambilini ukuthi i-thrombin ecushiwe i-PRP inyusa ukukhululwa kwama-molecule ezinto eziphilayo.Lezi zici zihlanganisa i-hepatocyte growth factor (HGF) kanye ne-tumor necrosis factor (TNF- α) , I-Transforming growth factor beta1 (TGF- β 1), i-vascular endothelial growth factor (VEGF) kanye ne-epidermis Growth factor (EGF).Olunye ucwaningo luye lwabonisa ukuthi i-PRP ikhuthaza ukwanda kohlobo lwe-i collagen namazinga e-aggrecan mRNA, kuyilapho kunciphisa ukuvinjelwa kwe-pro-inflammatory cytokine interleukin - (IL) 1 kubo.Kuphinde kwaphakanyiswa ukuthi ngenxa ye-HGF ne-TNF- α [28] i-PRP ingasiza ekusunguleni umphumela wokulwa nokuvuvukala.Womabili lawa malungiselelo amangqamuzana anciphisa i-nuclear factor kappaB (NF- κВ) Anti activation and expression;Okwesibili, ngokusebenzisa inkulumo ye-TGF- β 1 iphinde ivimbele i-monocyte chemotaxis, ngaleyo ndlela imelene ne-TNF- α Effect on the transactivation of chemokines.I-HGF ibonakala idlala indima ebalulekile kumphumela wokulwa nokuvuvukala obangelwa i-PRP.Le cytokine enamandla elwa nokuvuvukala ibhubhisa indlela yokubonisa i-NF- κ B kanye nenkulumo ye-cytokine ye-proinflammatory ivimbela impendulo yokuvuvukala.Ngaphezu kwalokho, i-PRP inganciphisa izinga eliphezulu le-nitric oxide (NO).Isibonelo, ku-articular cartilage, ukwanda kwe-NO concentration kuye kwafakazelwa ukuthi kuvimbela ukuhlanganiswa kwe-collagen futhi kubangele i-chondrocyte apoptosis, kuyilapho kukhulisa ukuhlanganiswa kwe-matrix metalloproteinases (MMPs), ngaleyo ndlela kukhuthaze ukuguqulwa kwe-catabolism.Ngokuphathelene nokuwohloka kwamangqamuzana, i-PRP iphinde icatshangwe ukuthi iyakwazi ukuphatha i-autophagy yezinhlobo ezithile zamaseli.Lapho efinyelela esimweni sokuguga sokugcina, amanye amaqembu amaseli alahlekelwa amandla okuba nesimo esimile nokuzivuselela.Kodwa-ke, ucwaningo lwakamuva lubonise ukuthi ukwelashwa kwe-PRP kungahlehlisa lezi zimo eziyingozi.UMoussa kanye nozakwabo bafakazele ukuthi i-PRP ingabangela ukuvikelwa kwama-chondrocyte ngokwandisa izimpawu ze-autophagy kanye ne-anti-inflammatory, kuyilapho kunciphisa i-apoptosis ye-cartilage yomuntu ye-osteoarthritis.U-Garcia Pratt et al.Kubikwa ukuthi i-autophagy inquma ukuguquka phakathi kwesiphetho sokuphumula nokuguga kwamangqamuzana e-muscle stem.Abacwaningi bakholelwa ukuthi, ku-vivo, ukujwayelekile kwe-autophagy edidiyelwe kugwema ukuqoqwa komonakalo we-intracellular futhi kuvimbela ukuguga nokusebenza kokuncipha kwamaseli e-satellite.Ngisho nasemangqamuzaneni e-stem yabantu asebekhulile, njengakamuva nje, u-Parrish noRodes nabo benze iminikelo ebalulekile, baphinde baveze amandla okulwa nokuvuvukala kwe-PRP.Ngalesi sikhathi, kugxilwe ekusebenzelaneni phakathi kwama-platelet nama-neutrophils.Ophenyweni lwabo, abacwaningi bachaza ukuthi ama-platelet acushiwe akhishwe yi-arachidonic acid amuncwa ama-neutrophils futhi aguqulwa abe ama-leukotrienes nama-prostaglandin, okungama-molecule aziwayo avuthayo.Kodwa-ke, ukusebenzisana kwe-platelet neutrophil kuvumela i-leukotriene ukuba iguqulwe ibe yi-lipoprotein, okuye kwafakazelwa ukuthi iyiprotheni ephumelelayo yokulwa nokuvuvukala enganciphisa ukusebenza kwe-neutrophils futhi ivimbele ukukhishwa kwe-dialysis, futhi ikhuthaze ifa esigabeni sokugcina se-cascade yokuphulukisa.
I-proinflammatory microenvironment iphazamisa inqubo yokuphulukisa.Okuyinkimbinkimbi kakhulu ukuthi umsebenzi ophezulu we-protease uvimbela isenzo semvelo se-growth factor (GF).Ngaphezu kwezakhiwo zayo ze-mitotic, angiogenic kanye ne-chemotactic, i-PRP iphinde ibe umthombo ocebile wezici eziningi zokukhula.Lawa ma-biomolecules angase alwe nemiphumela eyingozi ezicutshini ezivuvukalayo ngokulawula ukwanda kokuvuvukala nokusungula ukugqugquzelwa kwe-anabolic.
I-Cell Factor
Ama-Cytokines ku-PRP adlala indima ebalulekile ekuphatheni inqubo yokulungisa izicubu kanye nokulawula umonakalo ovuthayo.I-anti-inflammatory cytokines iwuhlu olubanzi lwama-molecule e-biochemical axhumanisa impendulo yama-cytokines ane-proinflammatory, ikakhulukazi ebangelwa ama-macrophage acushiwe.Ama-cytokine aphikisana nokuvuvukala asebenzisana nama-cytokine inhibitors athile kanye nama-soluble cytokine receptors ukulawula ukuvuvukala.I-Interleukin (IL) - I-1 receptor antagonists, i-IL-4, i-IL-10, i-IL-11 ne-IL-13 ihlukaniswa njengezidakamizwa eziyinhloko zokulwa nokuvuvukala, ama-cytokines.Ngokwezinhlobo ezihlukene zamanxeba, amanye ama-cytokines, afana ne-interferon, i-leukemia inhibitory factor, i-TGF- β kanye ne-IL-6, engabonisa imiphumela ye-proinflammatory noma anti-inflammatory.I-TNF-α, IL-1 ne-IL-18 ine-cytokine receptors ethile, engavimbela umphumela wokuvuvukala kwamanye amaprotheni [37].I-IL-10 ingenye yama-cytokines e-anti-inflammatory ephumelela kakhulu, engakwazi ukwehlisa ukulawula ama-cytokines e-proinflammatory afana ne-IL-1, IL-6 kanye ne-TNF- α， Futhi phezulu lawula izici eziphikisana nokuvuvukala.Lezi zindlela zokulwa nokulawula zidlala indima ebalulekile ekukhiqizweni nasekusebenzeni kwama-cytokines ane-proinflammatory.Ngaphezu kwalokho, ama-cytokines athile angase aqalise izimpendulo zesignali ezithile ukuze kukhuthazwe ama-fibroblasts, abalulekile ekulungiseni izicubu.I-cytokine evuthayo TGF β 1, IL-1 β, IL-6, IL-13 kanye ne-IL-33 ivuselela ama-fibroblasts ukuze ahlukanise abe yi-myofibroblasts futhi athuthukise i-ECM [38].Kanti, ama-fibroblasts akhiqiza i-cytokine TGF- β, IL-1 β, IL-33, CXC kanye ne-CC chemokines ikhuthaza ukusabela kokuvuvukala ngokuvula nokuqasha amangqamuzana omzimba omzimba njengama-macrophages.Lawa maseli avuvukalayo adlala izindima eziningi esilondeni, ikakhulukazi ngokukhuthaza ukukhululeka kwezilonda - kanye ne-biosynthesis yama-chemokines, ama-metabolites kanye nezici zokukhula, okubalulekile ekwakhiweni kabusha kwezicubu ezintsha.Ngakho-ke, ama-cytokines ku-PRP adlala indima ebalulekile ekukhuthazeni uhlobo lweseli lokuphendula lokuzivikela komzimba kanye nokukhuthaza ukuhlehla kwesiteji sokuvuvukala.Eqinisweni, abanye abacwaningi baqoke le nqubo ngokuthi "ukuvuvukala okuvuselelayo", okubonisa ukuthi isigaba sokuvuvukala, naphezu kokukhathazeka kwesiguli, kuyisinyathelo esidingekayo nesibucayi sokuphela okuphumelelayo kwenqubo yokulungisa izicubu, kucatshangelwa indlela ye-epigenetic ukuthi ukuvuvukala kubonisa. ukuthuthukisa i-cell plasticity.
Indima yama-cytokines ekuvuvukeni kwesikhumba sengane ibaluleke kakhulu ocwaningweni lomuthi ovuselelayo.Umehluko phakathi kwezinqubo zokuphulukisa ze-fetus kanye nezabantu abadala ukuthi izicubu ze-fetus ezilimele ngezinye izikhathi zibuyela esimweni sazo sangempela ngokuya ngeminyaka ye-fetus kanye nezinhlobo zezicubu ezifanele.Kubantu, isikhumba se-fetus singakhula ngokuphelele emasontweni angama-24, kanti kubantu abadala, ukuphulukiswa kwesilonda kungaholela ekwakhekeni kwezibazi.Njengoba sazi, uma kuqhathaniswa nezicubu ezinempilo, izakhiwo zemishini yezicubu ezibomvu ziyancipha kakhulu, futhi imisebenzi yazo ilinganiselwe.Ukunakwa okukhethekile kunikezwa i-cytokine IL-10, etholakala ivezwa kakhulu oketshezini lwe-amniotic kanye nesikhumba sombungu, futhi kuye kwafakazelwa ukuthi idlala indima ekulungisweni okungenazibazi kwesikhumba sengane, okukhuthazwa umphumela we-pleiotropic we-cytokine.ZgheibC et al.Ukufakelwa kwesikhumba sengane ku-transgenic knockout (KO) IL-10 amagundane kanye namagundane okulawula kwacwaningwa.Amagundane e-IL-10KO abonise izimpawu zokuvuvukala nokwakheka kwezibazi eduze kwama-graft, kuyilapho ama-graft eqenjini lokulawula abonisanga izinguquko eziphawulekayo ezicini ze-biomechanical futhi akukho ukuphulukiswa kwezibazi.
Ukubaluleka kokulawula ibhalansi ebucayi phakathi kokuvezwa kwama-cytokines aphikisana nokuvuvukala kanye ne-pro-inflammatory ukuthi yokugcina, lapho ekhiqizwa ngokweqile, ekugcineni ithumela izimpawu zokuwohloka kwamangqamuzana ngokunciphisa ukubonakaliswa kwezakhi zofuzo ezithile.Isibonelo, emithini ye-musculoskeletal, i-IL-1 β Down ilawula i-SOX9, enesibopho sokuthuthukiswa kwe-cartilage.I-SOX9 ikhiqiza izici ezibalulekile zokuloba zokuthuthukiswa kwe-cartilage, ilawula uhlobo lwe-II lwe-collagen alpha 1 (Col2A1), futhi inesibopho sokubhala ngekhodi uhlobo lwe-collagen yofuzo lwe-II.I-IL-1 β Ekugcineni, inkulumo ye-Col2A1 ne-aggrecan yehlisiwe.Kodwa-ke, ukwelashwa ngemikhiqizo ecebile ye-platelet kuye kwaboniswa ukuvimbela i-IL-1 β Kusengumngane onokwenzeka wemithi yokuvuselela ukuze kugcinwe ukubonakaliswa kwezakhi zofuzo ze-collagen futhi kunciphise i-apoptosis yama-chondrocyte ebangelwa ama-cytokines e-proinflammatory.
Ukugqugquzelwa kwe-Anabolic: Ngaphezu kokulawula isimo sokuvuvukala kwezicubu ezilimele, ama-cytokines ku-PRP nawo abambe iqhaza ekuphenduleni kwe-anabolic ngokudlala indima yawo ye-mitosis, ukukhangwa kwamakhemikhali nokwanda.Lolu ucwaningo lwe-in vitro oluholwa nguCavallo et al.Ukutadisha imiphumela ye-PRP ehlukene kuma-chondrocyte abantu.Abacwaningi baqaphele ukuthi imikhiqizo ye-PRP ene-platelet ephansi kanye nokugxila kwe-leukocyte ivuselela umsebenzi ojwayelekile we-chondrocyte, okulungele ukukhuthaza ezinye izindlela zamaselula zokuphendula kwe-anabolic.Isibonelo, ukuvezwa kohlobo ii-collagen kanye nokuhlanganisa ama-glycans kwabonwa.Ngokuphambene, ukugxila okuphezulu kwamaplatelet nama-leukocyte kubonakala kukhuthaza ezinye izindlela zokubonisa amaselula ezihlanganisa ama-cytokines ahlukahlukene.Ababhali basikisela ukuthi lokhu kungase kube ngenxa yokuba khona kwenani elikhulu lamangqamuzana amhlophe egazi kulokhu kwakhiwa kwe-PRP ethile.Lawa maseli abonakala ebophezelekile ekukhulumeni okungeziwe kwezinye izici zokukhula, njenge-VEGF, FGF-b, nama-interleukins i-IL-1b ne-IL-6, angase akhuthaze i-TIMP-1 ne-IL-10.Ngamanye amazwi, uma kuqhathaniswa nefomula “embi” ye-PRP, ingxube ye-PRP enothe ngamaplatelet namangqamuzana egazi amhlophe ibonakala ikhuthaza ukuhlasela okuhlobene kwama-chondrocyte.
Ucwaningo oluklanywe nguSchnabel et al.yaklanyelwe ukuhlola indima ye-autologous biomaterials kuzicubu ze-tendon yamahhashi.Ababhali baqoqa amasampula egazi namathenda avela kumahhashi amadala ayisithupha (iminyaka engu-2-4 ubudala), futhi bagxila ekutadisheni iphethini ye-gene expression, i-DNA kanye nokuqukethwe kwe-collagen ye-tendon explants ye-flexor digitorum superficialis yamahhashi akhuliswe phakathi nendawo equkethe i-PRP. noma eminye imikhiqizo yegazi.Ukukhishwa kwe-tendon kwakukhuliswe egazini, i-plasma, i-PRP, i-platelet deficient plasma (PPP) noma i-bone marrow aspirates (BMA), kanye nama-amino acids angeziwe ku-100%, i-50% noma i-10% ye-DMEM yamahhala ye-serum.Ekuqhubeni ukuhlaziya okusebenzayo kwe-biochemical ngemva…, abacwaningi baphawule ukuthi i-TGF- β Ukugxiliswa kwe-PDGF-BB ne-PDGF-1 ku-PRP medium kwakuphakeme kakhulu kunayo yonke eminye imikhiqizo yegazi ehloliwe.Ukwengeza, izicubu ze-tendon ezikhuliswe ku-100% PRP medium zibonise ukwanda kwezakhi zofuzo zamaprotheni e-matrix COL1A1, COL3A1 kanye ne-COMP, kodwa azizange zikhulise ama-enzyme e-catabolic MMPs3 kanye ne-13. Okungenani ngokwesakhiwo se-tendon, lokhu ku-vivo cwaningo kusekela ukusetshenziswa i-autolo - umkhiqizo wegazi we-gouty, noma i-PRP, yokwelapha i-tendinitis enkulu yezilwane ezincelisayo.
U-Chen et al.Umthelela wokwakha kabusha we-PRP kwaxoxwa ngawo futhi.Ochungechungeni lwabo lwangaphambili lwezifundo, abacwaningi bafakazele ukuthi, ngaphezu kokuthuthukisa ukwakheka kwe-cartilage, i-PRP iphinde yakhuthaza ukwanda kwe-ECM synthesis futhi yavimbela ukusabela kokuvuvukala kwe-articular cartilage kanye ne-nucleus pulposus.I-PRP ingenza kusebenze i-TGF ngokusebenzisa i-phosphorylation ye-Smad2/3- β Indlela yesiginali idlala indima ebalulekile ekukhuleni kweseli nokuhlukanisa.Ngaphezu kwalokho, kukholelwa ukuthi amahlule e-fibrin akhiwe ngemuva kokusebenza kwe-PRP ahlinzeka ngesakhiwo esiqinile se-dimensional, okwenza amangqamuzana abambelele, okungase kuholele ekwakhiweni kwezicubu ezintsha.
Abanye abacwaningi baye baba neqhaza elikhulu ekwelapheni izilonda zesikhumba ezingalapheki emkhakheni we-dermatology.Lokhu futhi kuyaphawuleka.Isibonelo, ucwaningo olwenziwa u-Hessler no-Shyam ngo-2019 lubonisa ukuthi i-PRP ibalulekile njengendlela yokwelapha engenzeka futhi ephumelelayo, kuyilapho isilonda esingamahlalakhona esingamelana nezidakamizwa sisaletha umthwalo omkhulu wezomnotho ekunakekelweni kwezempilo.Ikakhulukazi, isilonda sonyawo lwesifo sikashukela siyinkinga enkulu yezempilo eyaziwayo, eyenza izitho zomzimba kube lula ukunqunywa.Ucwaningo olushicilelwe ngu-Ahmed et al.ku-2017 kubonise ukuthi ijeli ye-PRP ye-autologous ingakhuthaza ukuphulukiswa kwesilonda ezigulini ezinezilonda zezinyawo zesifo sikashukela ngokukhulula izici ezidingekayo zokukhula, ngaleyo ndlela ithuthukise kakhulu izinga lokuphulukisa.Ngokufanayo, u-Gonchar kanye nozakwabo babuyekeze futhi baxoxisana ngamandla okuvuselela i-PRP kanye nama-cocktail factor factor ekwenzeni ngcono ukwelashwa kwezilonda ezinyaweni zesifo sikashukela.Abacwaningi bahlongoze ukuthi ukusetshenziswa kwezingxube zesici sokukhula kungenzeka kube yisixazululo esingenzeka, esingathuthukisa izinzuzo zokusebenzisa i-PRP kanye nesici esisodwa sokukhula.Ngakho-ke, uma kuqhathaniswa nokusetshenziswa kwesici esisodwa sokukhula, ukuhlanganiswa kwe-PRP namanye amasu okwelapha kungase kukhuthaze kakhulu ukuphulukiswa kwezilonda ezingapheli.
I-Fibrin
Ama-platelet aphethe izici eziningana ezihlobene nesistimu ye-fibrinolytic, engase ikhuphuke ilawule noma yehle ilawule ukusabela kwe-fibrinolytic.Ubudlelwano besikhathi kanye negalelo elihlobene lezingxenye ze-hematological kanye nomsebenzi we-platelet ekuwohlokeni kwehlule kuseyinkinga efanele ukuxoxwa okubanzi emphakathini.Izincwadi zethula izifundo eziningi ezigxile kuphela kumaplatelet, adume ngamandla awo okuthinta inqubo yokuphulukisa.Naphezu kwenani elikhulu lezifundo ezivelele, ezinye izingxenye ze-hematological, ezifana nezici ze-coagulation kanye nezinhlelo ze-fibrinolytic, nazo zitholakale zifaka isandla kakhulu ekulungiseni isilonda esisebenzayo.Ngokwencazelo, i-fibrinolysis iyinqubo eyinkimbinkimbi yezinto eziphilayo encike ekusebenzeni kwama-enzyme athile ukukhuthaza ukuwohloka kwe-fibrin.Ukusabela kwe-Fibrinolysis kuye kwahlongozwa abanye ababhali ukuthi imikhiqizo ye-fibrin degradation (fdp) ingase ibe ama-molecular agents anesibopho sokugqugquzela ukulungiswa kwezicubu.Ukulandelana kwezehlakalo ezibalulekile zebhayoloji ngaphambili kuvela ekufakweni kwe-fibrin nokususwa kwe-angiogenesis, okudingekayo ekwelapheni kwesilonda.Ukwakhiwa kwamahlule ngemva kokulimala kusebenza njengesendlalelo sokuvikela ukuvikela izicubu ekulahlekelweni kwegazi kanye nokuhlasela kwama-microbial agents, futhi kunikeza i-matrix yesikhashana lapho amangqamuzana angakwazi ukufuduka phakathi nenqubo yokulungisa.Ihlule libangelwa i-fibrinogen eqhekezwa yi-serine protease, futhi ama-platelet aqoqelwa ku-fibrin fiber mesh exhumene.Lokhu kusabela kwabangela ukwakheka kwe-polymerization ye-fibrin monomer, okuyisenzakalo esiyinhloko sokwakheka kwehlule legazi.Ihlule lingasetshenziswa futhi njengendawo yokugcina ama-cytokines nezici zokukhula, ezikhishwa ngesikhathi sokuwohloka kwamaplatelet acushiwe.Uhlelo lwe-fibrinolytic lulawulwa ngokuqinile yi-plasmin, futhi ludlala indima ebalulekile ekukhuthazeni ukufuduka kwamangqamuzana, i-bioavailability yezici zokukhula kanye nokulawulwa kwezinye izinhlelo ze-protease ezihilelekile ekuvuvukeni kwezicubu kanye nokuvuselelwa kabusha.Izingxenye ezibalulekile ze-fibrinolysis, njenge-urokinase plasminogen activator receptor (uPAR) kanye ne-plasminogen activator inhibitor-1 (PAI-1), zaziwa ngokuthi zivezwe kumaseli e-mesenchymal stem (MSCs), okuyizinhlobo zamaseli ezikhethekile ezidingekayo ukuze kupholeke isilonda ngempumelelo. .
Ukufuduka Kweseli
Ukusebenza kwe-plasminogen ngokusebenzisa inhlangano ye-UPA uPAR kuyinqubo ekhuthaza ukufuduka kwamangqamuzana avuthayo ngoba ithuthukisa i-extracellular proteinolysis.Ngenxa yokuntuleka kwezizinda ze-transmembrane kanye ne-intracellular, i-uPAR idinga ama-co receptors afana ne-integrin ne-vitellin ukuze ilawule ukufuduka kwamaseli.Iphinde yabonisa ukuthi ukuboshwa kwe-uPA uPAR kubangele ukwanda kokuhlobana kwe-uPAR ye-vitrectonectin ne-integrin, okukhuthaze ukunamathela kweseli.I-Plasminogen activator inhibitor-1 (PAI-1) yona yenza amaseli ahlukane.Uma ibophezela ku-uPA ye-uPA upar integrin complex endaweni yeseli, ibhubhisa ukusebenzisana phakathi kwe-upar vitellin ne-integrin vitellin.
Esimweni somuthi wokuvuselela kabusha, amaseli we-bone mesenchymal stem cell ahlanganiswa emnkantsheni uma kwenzeka umonakalo omkhulu wesitho, ngakho-ke angase atholakale ekusakazweni kweziguli ezinezithonjana eziningi.Kodwa-ke, ezimweni ezithile, njengokuhluleka kwe-renal ekupheleni kwesiteji, ukwehluleka kwesibindi sokuphela, noma ngesikhathi sokwenqatshwa ngemva kokufakelwa kwenhliziyo, lawa maseli angase angatholakali egazini [66].Kuyathakazelisa ukuthi lawa maseli wamathambo omuntu atholakala kumaseli we-mesenchymal (stromal) awakwazanga ukutholwa egazini labantu abanempilo [67].Iqhaza le-uPAR ekuhlanganiseni amaseli e-mesenchymal stem cell (BMSC) womnkantsha (BMSCs) liye lahlongozwa phambilini, okufana nokwenzeka kwe-uPAR ekuhlanganiseni ama-hematopoietic stem cell (HSCs).Varabaneni et al.Imiphumela yabonisa ukuthi ukusetshenziswa kwe-granulocyte colony-stimulating factor kumagundane ashodayo e-uPAR kubangele ukwehluleka kwe-MSC, okuphinde kwaqinisa indima esekelayo yohlelo lwe-fibrinolysis ekufudukeni kwamaseli.Ucwaningo olwengeziwe luphinde lwabonisa ukuthi i-glycosyl phosphatidylinositol egxilile e-uPA receptors ilawula ukunamathela, ukufuduka, ukwanda nokuhlukaniswa ngokwenza kusebenze izindlela ezithile zokusayina ze-intracellular, ngale ndlela elandelayo: i-phosphatidylinositol 4,5-diphosphate 3-kinase/Akt2 kanye ne-adhesion pathways1, (I-FAK).
Esimweni sokuphulukiswa kwesilonda se-MSC, isici se-fibrinolytic sibonise ukubaluleka kwayo okwengeziwe.Isibonelo, amagundane angenayo i-plasminogen abonise ukubambezeleka okukhulu ezenzakalweni zokuphulukisa amanxeba, okubonisa ukuthi i-plasmin yayibalulekile kule nqubo.Kubantu, ukulahleka kwe-plasmin nakho kungaholela ezinkingeni zokuphola kwesilonda.Ukuphazamiseka kokugeleza kwegazi kungavimbela kakhulu ukuvuselelwa kwezicubu, okubuye kuchaze ukuthi kungani lezi zinqubo zokuvuselela ziyinselele kakhulu ezigulini ezinesifo sikashukela.
Amaseli omnkantsha we-mesenchymal stem abuthwa endaweni yenxeba ukuze kusheshiswe ukuphola kwesilonda.Ngaphansi kwezimo ezinzile, lawa maseli azwakalisa i-uPAuPAR ne-PAI-1.Amaphrotheni amabili okugcina ayizici ze-hypoxia ezingaguquki α (HIF-1 α) Ukukhomba kulula kakhulu ngoba i-HIF-1 kuma-MSCs α Ukwenziwa kusebenze kwe-FGF-2 ne-HGF kukhuthaze ukulawulwa okuphezulu kwe-FGF-2 ne-HGF;I-HIF-2 α Ngokulandelayo, i-VEGF-A [77] ilawulwa phezulu, ehlangene enomthelela ekwelapheni kwesilonda,.Ukwengeza, i-HGF ibonakala ithuthukisa ukuqashwa kwamaseli we-stem mesenchymal womnkantsha ezindaweni zamanxeba ngendlela ehlangene.Kumele kuqashelwe ukuthi izimo ze-ischemic ne-hypoxic ziboniswe ukuthi ziphazamise kakhulu ukulungiswa kwesilonda.Yize ama-BMSC ejwayele ukuhlala ezicutshini ezihlinzeka ngamazinga aphansi komoyampilo, ukusinda kwama-BMSC atshalwe kabusha ku-vivo kuba nomkhawulo ngoba amaseli atshaliwe avame ukufa ngaphansi kwezimo ezimbi ezibonwa ezicutshini ezilimele.Isiphetho sokunamathela kanye nokuphila komnkantsha we-mesenchymal stem cell ngaphansi kwe-hypoxia kuncike ezintweni ze-fibrinolytic ezikhiqizwe yilawa maseli.I-PAI-1 inokuhlobana okuphezulu kwe-vitellin, ngakho-ke ingaqhudelana ngokubopha i-uPAR ne-integrin ku-vitellin, ngaleyo ndlela ivimbele ukunamathela kwamaseli nokufuduka.
I-Monocyte kanye nesistimu yokuvuselela kabusha
Ngokusho kwezincwadi, kunezingxoxo eziningi mayelana nendima ye-monocyte ekuphulukiseni isilonda.Ama-Macrophage ikakhulukazi avela kuma-monocyte egazi futhi adlala indima ebalulekile emithini yokuvuselela kabusha [81].Ngoba ama-neutrophils akhiqiza i-IL-4, IL-1, IL-6 ne-TNF- α, Lawa maseli ngokuvamile angena enxebeni cishe amahora angu-24-48 ngemva kokulimala.Ama-platelet akhulula i-thrombin ne-platelet factor 4 (PF4), engakhuthaza ukubuthwa kwama-monocyte futhi ahlukanise ama-macrophages namaseli e-dendritic.Isici esibalulekile sama-macrophage yi-plasticity yawo, okungukuthi, angakwazi ukuguqula ama-phenotypes futhi ahlukanise kwezinye izinhlobo zamangqamuzana, njengamangqamuzana e-endothelial, bese ebonisa imisebenzi ehlukene ezinhlobonhlobo ze-biochemical stimuli ku-microenvironment yesilonda.Amangqamuzana okuvuvukala aveza ama-phenotypes amabili amakhulu, i-M1 noma i-M2, kuye ngesignali ye-molecular yendawo njengomthombo wokuvuselela.I-M1 macrophages ibangelwa ama-microbial agents, ngakho-ke anemiphumela engaphezulu yokuvuvukala.Ngokuphambene, ama-macrophage e-M2 ngokuvamile akhiqizwa uhlobo lwe-2 ukusabela futhi anezindawo zokulwa nokuvuvukala, ngokuvamile ezibonakala ngokunyuka kwe-IL-4, IL-5, IL-9, ne-IL-13.Iphinde ihileleke ekulungiseni izicubu ngokukhiqizwa kwezinto ezikhulayo.Ukuguquka kusuka ku-M1 kuya ku-M2 subtype kuqhutshwa kakhulu isigaba sekwephuzile sokuphulukiswa kwesilonda.Ama-macrophage e-M1 aqala i-neutrophil apoptosis futhi aqalise ukucaciswa kwala maseli).I-phagocytosis ye-neutrophils ivuselela uchungechunge lwezenzakalo, lapho ukukhiqizwa kwama-cytokines kuvaliwe, i-macrophages i-polarizing futhi ikhulula i-TGF-β 1. Lesi sici sokukhula siyisilawuli esiyinhloko sokuhlukaniswa kwe-myofibroblast kanye nokuvinjelwa kwesilonda, okuvumela ukuxazulula ukuvuvukala nokuvuvukala. ukuqaliswa kwesigaba sokwanda endaweni yokuphulukisa [57].Enye iphrotheni ehlobene kakhulu ehilelekile ezinqubweni zamaselula i-serine (SG).Le hemopoietic cell secretory granule proteoglycan itholakale idingeka ukuze kugcinwe amaprotheni ayimfihlo kumaseli athile omzimba omzimba, njengama-mast cells, neutrophils nama-cytotoxic T lymphocyte.Nakuba amangqamuzana amaningi angewona ama-hematopoietic aphinde ahlanganise i-plasminogen, wonke amangqamuzana avuthayo akhiqiza inani elikhulu laleli phrotheni futhi aligcine kuma-granules ukuze aqhubeke nokusebenzisana nabanye abaxhumanisi abavuthayo, okuhlanganisa ama-protease, ama-cytokines, ama-chemokines nezici zokukhula.Amaketango e-glycosaminoglycan (GAG) afakwe icala elibi ku-SG abonakala ebaluleke kakhulu ekuzinzeni kwama-granules ayimfihlo, njengoba akwazi ukubophezela futhi enze kube lula ukugcinwa kwezingxenye ze-granular ezishajwa ngokuyisisekelo kuseli, iphrotheni, kanye nendlela eqondile yeketango le-GAG.Ngokuphathelene nokubamba iqhaza kwabo ocwaningweni lwe-PRP, u-Woulfe kanye nozakwabo baye babonisa ngaphambilini ukuthi ukuntuleka kwe-SG kuhlobene eduze nezinguquko ze-platelet morphological;I-Platelet factor 4 β- Amaphutha okugcinwa kwe-PDGF ku-thromboglobulin namaplatelet;Ukuhlanganiswa kweplatelet okungekuhle kanye nokukhiqizwa kwe-in vitro kanye nenkinga ye-thrombosis ku-vivo.Ngakho-ke abacwaningi baphetha ngokuthi le proteoglycan ibonakala iyisilawuli esiyinhloko se-thrombosis.
Imikhiqizo ecebile ye-Platelet ingathola igazi eliphelele lomuntu siqu ngokuqoqwa kanye ne-centrifugation, futhi ihlukanise ingxube ibe yizingqimba ezihlukene eziqukethe i-plasma, ama-platelet, amangqamuzana egazi amhlophe namangqamuzana egazi amhlophe.Uma ukugxila kweplatelet kungaphezu kwenani eliyisisekelo, kungasheshisa ukukhula kwethambo nezicubu ezithambile, kube nemiphumela engemihle emincane.Ukusetshenziswa kwemikhiqizo ye-PRP ezenzakalelayo kuyi-biotechnology esanda kuqhathaniswa, eye yabonisa ngokuqhubekayo imiphumela enethemba ekukhuthazeni nasekuthuthukiseni ukuphulukiswa kokulimala kwezicubu ezihlukahlukene.Ukusebenza kwale ndlela yokwelapha ehlukile kungase kubangelwe ekulethweni kwendawo kwezinhlobo eziningi zezinto ezikhulayo namaprotheni ukuze alingise futhi asekele ukuphulukiswa kwesilonda somzimba kanye nenqubo yokulungisa izicubu.Ngaphezu kwalokho, uhlelo lwe-fibrinolytic ngokusobala lunethonya elibalulekile kukho konke ukulungiswa kwezicubu.Ngaphezu kokuguqula ukubuthwa kwamangqamuzana avuvukalayo kanye namaseli amathambo e-mesenchymal stem cell, angakwazi futhi ukulawula umsebenzi we-proteolytic wezindawo zokuphulukisa amanxeba kanye nenqubo yokuvuselelwa kwezicubu ze-mesodermal, okuhlanganisa amathambo, uqwanga kanye nemisipha, ngakho-ke iyisici esibalulekile sokuphulukisa amanxeba. umuthi we-musculoskeletal.
Ukwelapha okusheshisiwe kuwumgomo ophishekelwa kakhulu ochwepheshe abaningi emkhakheni wezokwelapha.I-PRP imele ithuluzi elihle lebhayoloji, eliqhubeka nokuhlinzeka ngentuthuko ethembisayo ekukhuthazeni nasekuxhumaniseni i-cascade yezenzakalo ezivuselelayo.Kodwa-ke, ngenxa yokuthi leli thuluzi lokwelapha liseyinkimbinkimbi kakhulu, ikakhulukazi ngenxa yokuthi likhipha izinto ezingenakubalwa ze-bioactive kanye nezindlela zabo ezihlukahlukene zokusebenzisana kanye nemiphumela yokudlulisa isignali, ucwaningo olwengeziwe luyadingeka.
(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: Dec-16-2022