isibhengezo_sekhasi

I-Molecular Mechanism kanye nokusebenza kahle kwePlatelet-Rich Plasma (PRP) Intra-articular Therapy

I-Primary knee osteoarthritis (OA) isalokhu iyisifo esiwohlokayo esingalawuleki.Ngokukhula kobude besikhathi sokuphila kanye nobhubhane lokukhuluphala ngokweqile, i-OA ibangela umthwalo okhulayo wezomnotho nowomzimba.I-Knee OA yisifo esingelapheki se-musculoskeletal esingase sidinge ukungenelela kokuhlinzwa.Ngakho-ke, iziguli ziyaqhubeka nokufuna izindlela zokwelapha ezingahle zingasebenzi, njengokujova i-platelet-rich plasma (PRP) endaweni ehlangene yamadolo ethintekile.

Ngokuka-Jayaram et al., i-PRP iwukwelapha okuvelayo kwe-OA.Kodwa-ke, ubufakazi bomtholampilo bokusebenza kwayo busantuleka, futhi indlela yayo yokusebenza ayiqinisekile.Nakuba imiphumela ethembisayo iye yabikwa ngokuphathelene nokusetshenziswa kwe-PRP ku-Knee OA, imibuzo ebalulekile njengobufakazi obuqand’ ikhanda mayelana nokusebenza kwayo, ukulinganisa okujwayelekile, nezindlela ezinhle zokulungiselela azikaziwa.

I-Knee OA ilinganiselwa ukuthi izothinta ngaphezu kwe-10% yabantu bomhlaba, ngengozi yokuphila konke okungama-45%.Imihlahlandlela yesimanje incoma kokubili okungezona ezemithi (isb, ukuvivinya umzimba) kanye nokwelashwa kwemithi, njengemithi yomlomo engeyona i-steroidal eqeda ukuvuvukala (ama-NSAID).Nokho, lezi zindlela zokwelapha ngokuvamile zinezinzuzo zesikhashana kuphela.Ngaphezu kwalokho, ukusetshenziswa kwezidakamizwa ezigulini ezine-comorbidities kunqunyelwe ngenxa yengozi yezinkinga.

Ama-corticosteroids e-intra-articular ngokuvamile asetshenziselwa kuphela ukukhulula ubuhlungu besikhashana ngoba inzuzo yawo inqunyelwe emasontweni ambalwa, futhi imijovo ephindaphindiwe iboniswe ukuthi ihlotshaniswa nokulahlekelwa kwe-cartilage okwandisiwe.Abanye ababhali bathi ukusetshenziswa kwe-hyaluronic acid (HA) kuyimpikiswano.Kodwa-ke, abanye abalobi babike ukukhululeka kobuhlungu ngemva kwe-3 kuya ku-5 imijovo yamasonto onke ye-HA kumaviki angu-5 kuya kwangu-13 (ngezinye izikhathi kuze kufike ku-1 unyaka).

Uma ezinye izindlela ezingenhla zihluleka, i-knee arthroplasty (TKA) ngokuvamile inconywa njengokwelashwa okuphumelelayo.Kodwa-ke, kuyabiza futhi kungase kuhilele imiphumela emibi yezokwelapha kanye nangemuva kokuhlinzwa.Ngakho-ke, kubalulekile ukukhomba ezinye izindlela zokwelapha eziphephile nezisebenzayo ze-Knee OA.

Izindlela zokwelapha eziphilayo, ezifana ne-PRP, zisanda kuphenywa ukuze zokwelapha i-knee OA.I-PRP iwumkhiqizo wegazi ozenzakalelayo oneqoqo eliphezulu lamaplatelet.Ukusebenza kwe-PRP kucatshangwa ukuthi kuhlobene nokukhululwa kwezici zokukhula namanye ama-molecule, okuhlanganisa i-platelet-derived growth factor (PDGF), i-transforming growth factor (TGF) -beta, i-insulin-like growth factor type I (IGF-I) , kanye ne-vascular endothelial growth factor (VEGF).

Izincwadi eziningana zibonisa ukuthi i-PRP ingase ithembise ukwelashwa kwe-knee OA.Kodwa-ke, abaningi abavumelani ngendlela engcono kakhulu, futhi kunemikhawulo eminingi enciphisa ukuhlaziywa okufanele kwemiphumela yabo, engozini yokuchema.I-heterogeneity yezindlela zokulungiselela nezindlela zokujova ezisetshenziswe ezifundweni ezibikiwe kuwumkhawulo ekuchazeni uhlelo olufanele lwe-PRP.Ngaphezu kwalokho, izivivinyo eziningi zasebenzisa i-HA njengesiqhathanisi, okuyimpikiswano ngokwayo.Ezinye izivivinyo ziqhathanise i-PRP ne-placebo futhi zabonisa ukuthuthuka okungcono kakhulu kwezimpawu kunosawoti we-saline ezinyangeni eziyisi-6 neziyi-12.Kodwa-ke, lezi zinhlolo zinamaphutha amakhulu endlela yokusebenza, okuhlanganisa nokuntula ukuphuphuthekisa okufanele, okuphakamisa ukuthi izinzuzo zazo zingase zilinganiswe ngokweqile.

Izinzuzo ze-PRP zokwelashwa kwe-knee OA zimi kanje: kulula kakhulu ukuyisebenzisa ngenxa yokulungiswa kwayo okusheshayo kanye nokuhlasela okuncane;kuyindlela ethengekayo ngenxa yokusetshenziswa kwezinhlaka nezinsiza zezempilo zikahulumeni ezikhona;futhi kungenzeka ukuthi iphephile , ngoba iwumkhiqizo ozenzakalelayo.Okushicilelwe kwangaphambilini kubike kuphela izinkinga ezincane nezesikhashana.

Inhloso yalesi sihloko ukubukeza indlela yamanje yamangqamuzana yesenzo se-PRP kanye nobukhulu bokusebenza komjovo we-intra-articular we-PRP ezigulini ezine-knee OA.

 

Indlela ye-molecule yesenzo se-plasma ecebile ngeplatelet

I-Cochrane Library kanye ne-PubMed (MEDLINE) ifuna izifundo ezihlobene ne-PRI ku-knee OA zahlaziywa.Isikhathi sokusesha sisuka ekuqaleni kwenjini yokusesha kuya ku-December 15, 2021. Izifundo kuphela ze-PRP ku-Knee OA ababhali ababezibheka njengezithakazelisa kakhulu ezifakiwe.I-PubMed ithole ama-athikili angama-454, okungama-80 kuwo akhethiwe.Kutholwe i-athikili Kumtapo Wezincwadi we-Cochrane, nawo okhonjisiwe, onengqikithi yamareferensi angama-80.

Ucwaningo olushicilelwe ngo-2011 lubonise ukuthi ukusetshenziswa kwezinto zokukhula (amalungu e-TGF-β superfamily, umndeni we-fibroblast growth factor, i-IGF-I kanye ne-PDGF) ekulawuleni i-OA kubonakala kuthembisa.

Ngo-2014, uSandman et al.kubika ukuthi ukwelashwa kwe-PRP kwezicubu ezihlangene ze-OA kubangele ukwehla kwe-catabolism;noma kunjalo, i-PRP ibangele ukwehla okuphawulekayo kwe-matrix metalloproteinase 13, ukwanda kwenkulumo ye-hyaluronan synthase 2 kumaseli e-synovial, kanye nokwanda komsebenzi we-cartilage synthesis.Imiphumela yalolu cwaningo iphakamisa ukuthi i-PRP ivuselela ukukhiqizwa kwe-HA engapheli futhi inciphisa i-cartilage catabolism.I-PRP iphinde ivimbele ukuhlushwa kwabaxhumanisi abavuthayo kanye ne-gene expression in synovial and chondrocytes.

Ku-2015, ucwaningo lwelabhorethri olulawulwayo lubonise ukuthi i-PRP ikhuthaze kakhulu ukwanda kwamangqamuzana kanye nokugcinwa kwamaprotheni ebusweni ku-cartilage yamadolo omuntu kanye namaseli e-synovial.Lokhu kubheka kusiza ukuchaza izindlela ze-biochemical ezihlobene nokusebenza kwe-PRP ekwelapheni i-knee OA.

Kumodeli ye-murine OA (isifundo selabhorethri elawulwayo) ebikwe nguKhatab et al.Ngo-2018, imijovo eminingi yokukhipha i-PRP inciphise ubuhlungu nokushuba kwe-synovial, okungenzeka ukuthi ixhunywe yi-macrophage subtypes.Ngakho-ke, le mijovo ibonakala inciphisa ubuhlungu nokuvuvukala kwe-synovial, futhi ingase ivimbele ukukhula kwe-OA ezigulini ezine-OA yesigaba sokuqala.

Ngo-2018, ukubuyekezwa kwezincwadi ze-database ye-PubMed kwaphetha ngokuthi ukwelashwa kwe-PRP kwe-OA kubonakala kusebenzisa umphumela wokulinganisa endleleni ye-Wnt/β-catenin, okungase kubaluleke kakhulu ekufezeni imiphumela yayo yomtholampilo enenzuzo.

Ngo-2019, uLiu et al.uphenye indlela yamangqamuzana lapho ama-exosome asuselwa ku-PRP abandakanyeka ekwehliseni i-OA.Kubalulekile ukugqamisa ukuthi ama-exosome adlala indima ebalulekile ekuxhumaneni kwe-intercellular.Kulolu cwaningo, ama-chondrocyte onogwaja oyinhloko ahlukaniswa futhi aphathwa nge-interleukin (IL) -1β ukuze kusungulwe imodeli ye-in vitro ye-OA.Ukwanda, ukufuduka, kanye nokuhlolwa kwe-apoptosis kukalwa futhi kwaqhathaniswa phakathi kwama-exosome asuselwa ku-PRP kanye ne-PRP eyenziwe yasebenza ukuze kuhlolwe umphumela wokwelapha ku-OA.Izindlela ezihilelekile kumzila wokusayina we-Wnt/β-catenin zaphenywa ngokuhlaziywa kwe-blot yasentshonalanga.Ama-exosome asuselwa ku-PRP atholwe anemiphumela yokwelapha efanayo noma engcono ku-OA kune-PRP ecushiwe ye-in vitro kanye ne-vivo.

Kumodeli yegundane ye-posttraumatic OA eyabikwa ngo-2020, u-Jayaram et al.basikisela ukuthi imiphumela ye-PRP ekuqhubekeleni phambili kwe-OA kanye ne-hyperalgesia ebangelwa izifo ingase ibe yi-leukocyte-dependent.Baphinde basho ukuthi i-leukocyte-poor PRP (LP-PRP) kanye nenani elincane le-leukocyte-rich PRP (LR-PRP) ivimbela ivolumu nokulahlekelwa kwendawo.

Okutholakele kubikwe nguYang et al.Ucwaningo lwe-2021 lubonise ukuthi i-PRP okungenani inciphise kancane i-IL-1β-induced chondrocyte apoptosis nokuvuvukala ngokuvimbela i-hypoxia-inducible factor 2α.

Kumodeli yegundane ye-OA esebenzisa i-PRP, i-Sun et al.I-microRNA-337 kanye ne-microRNA-375 kutholwe ukubambezela ukuqhubeka kwe-OA ngokuthinta ukuvuvukala kanye ne-apoptosis.

Ngokusho kukaSheean et al., imisebenzi ye-biological ye-PRP inezici eziningi: i-platelet alpha granules ikhuthaza ukukhululwa kwezici ezihlukahlukene zokukhula, kuhlanganise ne-VEGF ne-TGF-beta, futhi ukuvuvukala kulawulwa ngokuvimbela indlela ye-nuclear factor-κB.

Ukugxila kwezinto ezihlekisayo ku-PRP okulungiselelwe kusuka kokubili kits kanye nemiphumela yezinto ezihlekisayo ku-macrophage phenotype kwaphenywa.Bathole umehluko ezingxenyeni zamaselula kanye nokugxila kwe-humoral factor phakathi kwe-PRP ehlanjululwe kusetshenziswa amakhithi amabili.Ikhithi ye-autologous protein solution LR-PRP inokugxila okuphezulu kwe-M1 kanye ne-M2 nezici ezihlobene ne-macrophage.Ukwengezwa kwe-PRP supernatant ku-culture medium of monocyte-derived macrophages kanye ne-M1 polarized macrophages kubonise ukuthi i-PRP ivimbele i-M1 macrophage polarization futhi yakhuthaza i-M2 macrophage polarization.

Ngo-2021, uSzwedowski et al.Izici zokukhula ezikhishwe emajoyini amadolo e-OA ngemva komjovo we-PRP zichazwa: i-tumor necrosis factor (TNF), i-IGF-1, i-TGF, i-VEGF, i-disaggregate, ne-metalloproteinase ene-thrombospondin motifs, i-interleukins, i-matrix metalloproteinases, isici sokukhula kwe-epidermal, ukukhula kwe-hepatocyte, i-fibroblast. ukukhula, ukukhula kwe-keratinocyte kanye ne-platelet factor 4.

1. I-PDGF

I-PDGF yatholwa okokuqala kuma-platelet.Kuyi-polypeptide ekwazi ukumelana nokushisa, ukumelana ne-asidi, i-cationic polypeptide ekhishwa kalula nge-trypsin.Ingenye yezinto zokuqala zokukhula ezivela kumasayithi okuphuka.Ivezwa kakhulu ezicutshini zamathambo ezibuhlungu, okwenza i-osteoblasts i-chemotactic futhi ikhule, ikhulise ikhono le-collagen synthesis, futhi ikhuthaze ukumuncwa kwama-osteoclasts, ngaleyo ndlela ikhuthaze ukwakheka kwamathambo.Ngaphezu kwalokho, i-PDGF ingaphinde ikhuthaze ukwanda nokuhlukaniswa kwama-fibroblasts futhi ikhuthaze ukulungiswa kabusha kwezicubu.

2. TGF-B

I-TGF-B iyi-polypeptide eyakhiwe ngamaketanga angu-2, esebenza kuma-fibroblasts kanye nama-pre-osteoblasts ku-paracrine kanye/noma ifomu le-autocrine, evuselela ukwanda kwama-osteoblasts nama-pre-osteoblasts kanye nokuhlanganiswa kwe-collagen fibers, njenge-chemokine, i-osteoprogenitor. amangqamuzana adonswa esicutshini sethambo elimele, futhi ukwakheka nokumuncwa kwama-osteoclast kuyavinjelwa.I-TGF-B iphinde ilawule ukuhlanganiswa kwe-ECM (i-extracellular matrix), inemiphumela ye-chemotactic kuma-neutrophils nama-monocyte, futhi ilamula izimpendulo zendawo zokuvuvukala.

3. I-VEGF

I-VEGF iyi-dimeric glycoprotein, ebophezela kuma-receptors ebusweni bamaseli e-vascular endothelial ngokusebenzisa i-autocrine noma i-paracrine, ikhuthaza ukwanda kwamangqamuzana e-endothelial, ibangele ukwakheka nokusungulwa kwemithambo yegazi emisha, inikeze umoya-mpilo emaphethelweni okuphuka, inikeza izakhi, futhi ithuthe imfucumfucu ye-metabolic. ., ukuhlinzeka nge-microenvironment efanelekayo ye-metabolism endaweni yokuvuselela amathambo wendawo.Bese, ngaphansi kwesenzo se-VEGF, umsebenzi we-alkaline phosphatase wokuhlukaniswa kwe-osteoblast uyathuthukiswa, futhi usawoti wendawo we-calcium uyafakwa ukuze kuthuthukiswe ukuphulukiswa kokuphuka.Ngaphezu kwalokho, i-VEGF ikhuthaza ukulungiswa kwezicubu ezithambile ngokwenza ngcono ukunikezwa kwegazi kwezicubu ezithambile ezizungeze ukuphuka, futhi ikhuthaze ukuphulukiswa kokuphuka, futhi inomphumela wokukhuthazana nge-PDGF.

4. EGF

I-EGF iyisici esikhuthazayo se-cell division esikhuthaza ukuhlukana nokwanda kwezinhlobo ezihlukahlukene zamangqamuzana ezicubu emzimbeni, kuyilapho ikhuthaza ukwakheka kwe-matrix nokubekwa kwayo, ikhuthaza ukwakheka kwezicubu ze-fibrous, futhi iqhubeka nokushintsha ibe ithambo ukuze ithathele indawo ukwakheka kwezicubu zethambo.Esinye isici i-EGF ebamba iqhaza ekulungiseni ukuphuka ukuthi ingenza i-phospholipase A isebenze, ngaleyo ndlela ikhuthaze ukukhululwa kwe-arachidonic acid kumaseli e-epithelial, futhi ikhuthaze ukuhlanganiswa kwe-prostaglandin ngokulawula imisebenzi ye-cyclooxygenase ne-lipoxygenase.Indima ye-resorption kanye nokwakheka kwamathambo kamuva.Kungabonakala ukuthi i-EGF ibamba iqhaza enqubweni yokuphulukisa yokuphuka futhi ingasheshisa ukuphulukiswa kokuphuka.Ngaphezu kwalokho, i-EGF ingakhuthaza ukwanda kwamangqamuzana e-epidermal kanye namaseli e-endothelial, futhi yenze amangqamuzana e-endothelial athuthele endaweni yesilonda.

5. IGF

I-IGF-1 iyi-polypeptide ye-single-chain ebopha kuma-receptors ethanjeni futhi isebenze i-tyrosine protease ngemva kwe-autophosphorylation ye-receptor, ekhuthaza i-phosphorylation ye-insulin receptor substrates, ngaleyo ndlela ilawula ukukhula kwamangqamuzana, ukwanda kanye ne-metabolism.Ingavuselela ama-Osteoblasts nama-pre-osteoblasts, ikhuthaze uqwanga nokwakheka kwe-bone matrix.Ngaphezu kwalokho, idlala indima ebalulekile ekuhlanganiseni ukuguqulwa kwamathambo ngokuxhumanisa ukuhlukaniswa nokwakhiwa kwama-osteoblasts nama-osteoclasts kanye nemisebenzi yabo yokusebenza.Ngaphezu kwalokho, i-IGF ingenye yezinto ezibalulekile ekulungiseni amanxeba.Kuyisici esikhuthaza ukungena kwe-fibroblasts emjikelezweni weseli futhi ikhuthaze ukuhlukaniswa nokuhlanganiswa kwe-fibroblasts.

 

I-PRP i-autologous concentrate yamaplatelet kanye nezici zokukhula ezitholakala egazini le-centrifuged.Kunezinye izinhlobo ezimbili ze-platelet concentrates: i-platelet-rich fibrin kanye ne-plasma-rich growth factor.I-PRP ingatholakala kuphela egazini eliwuketshezi;akunakwenzeka ukuthola i-PRP ku-serum noma igazi elijiyile.

Kunamasu ahlukene okuhweba okuqoqa igazi nokuthola i-PRP.Umehluko phakathi kwabo uhlanganisa nenani legazi elidinga ukukhishwa esigulini;indlela yokuzihlukanisa;isivinini se-centrifugation;inani lokugxilisa ivolumu ngemva kwe-centrifugation;isikhathi sokucubungula;

Izindlela ezihlukene ze-centrifugation yegazi ziye zabikwa ukuthi zithinta isilinganiso se-leukocyte.Izinombolo zamaplatelet ku-1 μL wegazi kubantu abanempilo zisuka ku-150,000 kuye ku-300,000.Ama-platelet anesibopho sokumisa ukopha.

Ama-alpha granules amaplatelet aqukethe izinhlobo ezihlukene zamaphrotheni njengezici zokukhula (isb. ukuguqula i-beta factor beta, i-insulin-like growth factor, i-epidermal growth factor), ama-chemokines, ama-coagulant, ama-anticoagulant, amaprotheni e-fibrinolytic, amaprotheni okunamathela, amaphrotheni e-Integral membrane, abaxhumanisi bomzimba. , izici ze-angiogenic kanye nama-inhibitors, namaprotheni abulala amagciwane.

Indlela eqondile yesenzo se-PRP ayikaziwa.I-PRP ibonakala ivuselela ama-chondrocyte ukulungisa kabusha i-cartilage kanye ne-biosynthesis ye-collagen ne-proteoglycans.Isetshenziswe ezicini ezihlukahlukene zezokwelapha ezifana nokuhlinzwa komlomo kanye ne-maxillofacial (okuhlanganisa i-temporomandibular OA), i-dermatology, i-ophthalmology, ukuhlinzwa kwe-cardiothoracic kanye nokuhlinzwa kwepulasitiki.

 

(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: Jul-27-2022