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Molecular Mechanism uye Kubudirira kwePlatelet-Rich Plasma (PRP) Intra-articular Therapy

Primary knee osteoarthritis (OA) inoramba iri chirwere chisingachinjiki chinodzikira.Nekuwedzera kwekugara kwehupenyu uye chirwere chekufutisa, OA iri kukonzera kukura kwehupfumi uye mutoro wemuviri.Knee OA chirwere chisingaperi chemusculoskeletal chinogona kupedzisira chichida kupindira kwekuvhiya.Nokudaro, varwere vanoramba vachitsvaga mishonga isingagadziriswi, yakadai sejojo ​​yeplatelet-rich plasma (PRP) mumabvi akabatanidzwa.

Sekureva kwaJayaram et al., PRP kurapwa kuri kubuda kweOA.Zvisinei, uchapupu hwekiriniki hwekushanda kwayo huchiri kushayikwa, uye maitiro ayo ekuita haana chokwadi.Kunyange zvazvo migumisiro yakavimbiswa yakave yakashumwa maererano nekushandiswa kwePRP mumabvi OA, mibvunzo inokosha yakadai sehumbowo hunogutsa maererano nekubudirira kwayo, madhigirii akaenzana, uye maitiro akanaka ekugadzirira anoramba asingazivikanwi.

Knee OA inofungidzirwa kubata chikamu chinodarika gumi kubva muzana chehuwandu hwepasi rose, nenjodzi yehupenyu hwe45%.Mitemo yemazuva ano inokurudzira zvose zvisiri zvemishonga (semuenzaniso, kurovedza muviri) uye mishonga yemishonga, yakadai semuromo nonsteroidal anti-inflammatory drugs (NSAIDs).Zvisinei, marapiro aya anowanzova nezvinobatsira zvenguva pfupi chete.Uyezve, kushandiswa kwezvinodhaka kune varwere vane comorbidities kunogumira nekuda kwengozi yezvinetso.

Intra-articular corticosteroids inowanzoshandiswa chete pakuderedza marwadzo kwenguva pfupi nokuti kubatsirwa kwavo kunogumira kumavhiki mashomanana, uye majekiseni akadzokororwa akaratidzwa akabatanidzwa nekuwedzera kwekurasika kwekatekete.Vamwe vanyori vanotaura kuti kushandiswa kwehyaluronic acid (HA) kune nharo.Zvisinei, vamwe vanyori vakarondedzera marwadzo mushure me3 kusvika ku5 majekiseni evhiki nevhiki eHA kwemavhiki mashanu kusvika kumavhiki e13 (dzimwe nguva kusvika ku1 gore).

Kana dzimwe nzira dziri pamusoro apa dzakundikana, zvachose ibvi arthroplasty (TKA) inowanzokurudzirwa semushonga unoshanda.Zvisinei, inodhura uye inogona kusanganisira mishonga uye postoperative yakashata migumisiro.Naizvozvo, zvakakosha kuona mamwe marapirwo akachengeteka uye anoshanda emabvi OA.

Biological therapies, sePRP, ichangobva kuongororwa kuitira kurapwa kwebvi OA.PRP chigadzirwa cheropa che autologous chine huwandu hwakawanda hwemaplatelet.Kubudirira kwePRP kunofungidzirwa kuti kwakabatana nekusunungurwa kwekukura kwezvinhu uye mamwe mamorekuru, kusanganisira platelet-derived growth factor (PDGF), kushandura kukura factor (TGF) -beta, insulin-like growth factor type I (IGF-I) , uye vascular endothelial growth factor (VEGF).

Zvinyorwa zvakawanda zvinoratidza kuti PRP inogona kunge ichivimbisa kurapwa kwebvi OA.Zvisinei, vazhinji havabvumirani pamusoro penzira yakanakisisa, uye pane zvakawanda zvinogumira zvinoderedza kuongororwa kwakakodzera kwemigumisiro yavo, pangozi yekusarura.Iyo heterogeneity yegadziriro uye nzira dzejekiseni dzinoshandiswa muzvidzidzo zvakashumwa iganhuriro mukutsanangura yakanakira PRP system.Uyezve, miedzo yakawanda yakashandisa HA semuenzanisi, izvo zvinonetsa pachazvo.Mimwe miedzo yakaenzanisa PRP ne placebo uye yakaratidza zviri nani zviratidzo zvekuvandudza pane saline pa6 uye 12 mwedzi.Nekudaro, iyi miedzo ine zvakati wandei kukanganisa kwemaitiro, kusanganisira kushaikwa kwekupofumadza kwakaringana, zvichiratidza kuti mabhenefiti avo anogona kuve akawandisa.

Zvakanakira zvePRP zvekurapa kwebvi OA ndezvizvi: zviri nyore kushandisa nekuda kwekukurumidza kugadzirira uye kushoma kupindira;inzira inokwanisika nekuda kwekushandiswa kwezvimiro zvebasa rehutano hweveruzhinji nemidziyo;uye inogona kunge yakachengeteka, nekuti chigadzirwa che autologous.Zvinyorwa zvakapfuura zvakangoshuma matambudziko madiki uye echinguvana.

Chinangwa chechinyorwa ichi ndechekuongorora ikozvino ma molecular maitiro ekuita kwePRP uye chiyero chekushanda kwe-intra-articular injection yePRP kune varwere vane mabvi OA.

 

Molecular maitiro ekuita kweplatelet-rich plasma

The Cochrane Library uye PubMed (MEDLINE) inotsvaga zvidzidzo zvine chokuita nePRI mumabvi OA zvakaongororwa.Nguva yekutsvaga inobva pakutanga kwejini yekutsvaga kusvika kuDecember 15, 2021. Zvidzidzo chete zvePRP mumabvi OA izvo vanyori vaifunga kuti vanofarira zvikuru zvakabatanidzwa.PubMed yakawana zvinyorwa zve454, izvo makumi masere zvakasarudzwa.Chinyorwa chakawanikwa muCochrane Library, iyo zvakare yakarongedzerwa, ine huwandu hwemakumi masere mareferensi.

Chidzidzo chakabudiswa muna 2011 chakaratidza kuti kushandiswa kwekukura kwezvinhu (nhengo dzeTGF-β superfamily, fibroblast growth factor family, IGF-I uye PDGF) muhutungamiri hweOA inoratidzika kuva inovimbisa.

Muna 2014, Sandman et al.yakashuma kuti PRP kurapwa kweOA joint tissue yakaguma nekuderera kwe catabolism;zvisinei, PRP yakaguma nekuderera kukuru kwematrix metalloproteinase 13, kuwedzera kwe hyaluronan synthase 2 kutaura mumasero e synovial, uye kuwedzera kwebasa rekugadzira cartilage.Migumisiro yechidzidzo ichi inoratidza kuti PRP inokurudzira kugadzirwa kweEndogenous HA uye inoderedza cartilage catabolism.PRP yakadzivisawo kukanganiswa kwevamiririri vanovhiringidza uye maitiro avo ejeni mu synovial uye chondrocytes.

Muna 2015, chidzidzo cherabhoritari chinodzorwa chakaratidza kuti PRP yakakurudzira zvakanyanya kuwedzera kwesero uye pamusoro peprotein secretion mumabvi emabvi cartilage uye synovial masero.Aya maonesheni anobatsira kutsanangura nzira dzebiochemical dzakabatanidzwa nekubudirira kwePRP mukurapa kwemabvi OA.

Mune murine OA modhi (inodzorwa laboratory kudzidza) yakataurwa naKhatab et al.Muna 2018, majekiseni akawanda ePRP ekusunungura akaderedza marwadzo uye kukora kwe synovial, zvichida yakapindirana ne macrophage subtypes.Nekudaro, majekiseni aya anoita seanoderedza marwadzo uye kuzvimba kwe synovial, uye anogona kutadzisa OA kukura muvarwere vane nhanho yekutanga OA.

Muna 2018, ongororo yePubMed dhatabhesi mabhuku yakagumisa kuti PRP kurapwa kweOA inoratidzika kunge ine modulating mhedzisiro paWnt/β-catenin nzira, iyo inogona kuve yakakosha pakuwana yayo inobatsira kliniki mhedzisiro.

Muna 2019, Liu et al.yakaongorora iyo molecular mechanism iyo PRP-yakatorwa exosomes inobatanidzwa mukuderedza OA.Izvo zvakakosha kuratidza kuti exosomes inoita basa rakakosha mukutaurirana kweintercellular.Muchidzidzo ichi, primary rabbit chondrocytes yakaparadzaniswa uye yakabatwa ne interleukin (IL) -1β kuti igadzire in vitro model yeOA.Kuwedzera, kutama, uye apoptosis assays akayerwa uye akaenzaniswa pakati pePRP-yakatorwa exosomes uye yakagadziriswa PRP kuti iongorore maitiro ekurapa paOA.Nzira dzakabatanidzwa muWnt / β-catenin chiratidzo chenzira dzakaongororwa neWestern blot analysis.PRP-yakatorwa exosomes yakawanikwa iine zvakafanana kana zviri nani kurapa mhedzisiro paOA pane activated PRP in vitro uye in vivo.

Mune mbeva modhi yeposttraumatic OA yakataurwa muna 2020, Jayaram et al.zvinoratidza kuti migumisiro yePRP paOA kufambira mberi uye chirwere-chinokonzera hyperalgesia inogona kuva leukocyte-inotenderera.Vakataurawo kuti leukocyte-varombo PRP (LP-PRP) uye shoma shoma ye-leukocyte-rich PRP (LR-PRP) inodzivirira huwandu uye kurasikirwa kwepamusoro.

Zvakawanikwa zvakataurwa naYang et al.Chidzidzo che2021 chakaratidza kuti PRP inenge yakadzivirirwa zvishoma IL-1β-induced chondrocyte apoptosis uye kuzvimba nekudzivisa hypoxia-inducible factor 2α.

Mune mbeva modhi yeOA uchishandisa PRP, Zuva et al.microRNA-337 uye microRNA-375 zvakawanikwa kunonoka OA kufambira mberi nekukanganisa kuzvimba uye apoptosis.

Maererano naSheean et al., zviitiko zvehupenyu zvePRP zvakasiyana-siyana: platelet alpha granules inokurudzira kusunungurwa kwezvinhu zvakasiyana-siyana zvekukura, kusanganisira VEGF uye TGF-beta, uye kuzvimba kunotungamirirwa nekudzivisa nyukliya-κB nzira.

Mafungiro ehumoral factor muPRP yakagadzirirwa kubva kune ese makiti uye mhedzisiro yehumoral zvinhu pane macrophage phenotype zvakaongororwa.Vakawana misiyano muzvikamu zvemasero uye humoral factor concentrations pakati pePRP yakacheneswa vachishandisa makiti maviri.Iyo autologous protein solution LR-PRP kit ine yakanyanya kuwanda kweM1 uye M2 macrophage-ane hukama zvinhu.Kuwedzerwa kwePRP supernatant kune tsika yepakati ye monocyte-yakagadzirwa macrophages uye M1 polarized macrophages yakaratidza kuti PRP yakadzivisa M1 macrophage polarization uye yakakurudzira M2 macrophage polarization.

Muna 2021, Szwedowski et al.Kukura kwezvinhu zvakaburitswa muOA mabvi majoini mushure mePRP jekiseni zvinotsanangurwa: tumor necrosis factor (TNF), IGF-1, TGF, VEGF, disaggregate, uye metalloproteinases ine thrombospondin motifs, interleukins, matrix metalloproteinases, epidermal growth factor, hepatocyte kukura, fibroblast. kukura chinhu, keratinocyte kukura chinhu uye platelet factor 4.

1. PDGF

PDGF yakatanga kuwanikwa mumaplatelet.Iyo inodzivirira kupisa, acid-resistant, cationic polypeptide iyo inogadzika nyore hydrolyzed ne trypsin.Ndiyo imwe yezvekutanga kukura zvinhu zvinoonekwa munzvimbo dzakaputsika.Inonyanya kuratidzwa mukukuvara kwemapfupa emapfupa, izvo zvinoita kuti osteoblasts chemotactic uye iwedzere, inowedzera kukwanisa kwe collagen synthesis, uye inokurudzira kubatwa kweosteoclasts, nokudaro inokurudzira kuumbwa kwemapfupa.Mukuwedzera, PDGF inogonawo kukurudzira kuwanda uye kusiyanisa kwe fibroblasts uye kukurudzira kugadziriswa kwetishu.

2. TGF-B

TGF-B inonzi polypeptide inoumbwa neketani mbiri, iyo inoshanda pa fibroblasts uye pre-osteoblasts muparacrine uye / kana autocrine fomu, inokurudzira kuwanda kwe osteoblasts uye pre-osteoblasts uye synthesis ye collagen fibers, se chemokine, the osteoprogenitor. masero anopinzwa munyama yakakuvara yemapfupa, uye kuumbwa uye kutorwa kweosteoclasts kunodzivirirwa.TGF-B inodzorawo ECM (extracellular matrix) synthesis, ine chemotactic mhedzisiro pane neutrophils uye monocytes, uye inopindirana nekuzvimba mhinduro dzemuno.

3. VEGF

VEGF inonzi dimeric glycoprotein, inosunga kune zvinogamuchirwa pamusoro pevascular endothelial masero kuburikidza ne autocrine kana paracrine, inosimudzira endothelial cell proliferation, inokurudzira kuumbwa uye kugadzwa kwemidziyo yeropa mitsva, inopa okisijeni kumigumo yekuputsika, inopa zvinovaka muviri, uye inotakura tsvina yemetabolism. ., kupa microenvironment yakanaka yemetabolism munharaunda yekuvandudza mapfupa emunharaunda.Zvadaro, pasi pechiito cheVEGF, iyo alkaline phosphatase ye osteoblast kusiyanisa inowedzerwa, uye yemuno calcium salt inoiswa kuti ikurudzire kuporeswa kwekutyoka.Pamusoro pezvo, VEGF inosimudzira kugadziriswa kwematishu akapfava nekuvandudza kupihwa kweropa kwezvinyoro zvinyoro zvakatenderedza pakatyoka, uye inosimudzira kuporeswa kwekutyoka, uye ine kusimudzira pamwe nePDGF.

4. EGF

EGF isimba rine simba sero rinosimudzira chinhu chinosimudzira kupatsanurwa uye kuwanda kwemhando dzakasiyana siyana dzematishu masero mumuviri, uku ichikurudzira matrix synthesis uye deposition, ichikurudzira fibrous tishu kuumbwa, uye kuramba ichichinja kuita pfupa kutsiva pfupa kuumbwa kwetishu.Chimwe chinhu icho EGF inobatanidzwa mukugadzirisa kuputsika ndechokuti inogona kuita phospholipase A, nokudaro ichikurudzira kusunungurwa kwearachidonic acid kubva mumasero epithelial, uye kukurudzira kuumbwa kweprostaglandin nekugadzirisa mabasa e cyclooxygenase uye lipoxygenase.Basa re resorption uye gare gare kuumbwa kwemapfupa.Zvinogona kuonekwa kuti EGF inotora chikamu mukurapa kwekutyoka uye inogona kukurumidza kuporesa kuputsika.Mukuwedzera, EGF inogona kukurudzira kupararira kwemasero epidermal uye endothelial masero, uye kuita kuti endothelial masero aende kune ronda pamusoro.

5. IGF

IGF-1 i-single-chain polypeptide inosunga kune zvinogamuchirwa mumapfupa uye inoshandisa tyrosine protease mushure mekugamuchira autophosphorylation, iyo inokurudzira phosphorylation ye insulin receptor substrates, nokudaro inodzora sero kukura, kupararira uye metabolism.Inogona kukurudzira Osteoblasts uye pre-osteoblasts, kukurudzira cartilage uye bone matrix kugadzirwa.Mukuwedzera, inobata basa rinokosha mukubatana kwekugadzirisa pfupa kuburikidza nekugadzirisa kusiyanisa uye kuumbwa kwe osteoblasts uye osteoclasts nemabasa avo anoshanda.Mukuwedzera, IGF zvakare chimwe chezvinhu zvakakosha pakugadzirisa maronda.Icho chinhu chinokurudzira kupinda kwe fibroblasts mukati mesero cycle uye inokurudzira kusiyanisa uye synthesis ye fibroblasts.

 

PRP ndeye autologous concentrate yemaplatelet uye kukura kwezvinhu zvakatorwa kubva muropa recentrifuged.Kune mamwe marudzi maviri eplatelet concentrates: platelet-rich fibrin uye plasma-rich growth factor.PRP inogona kuwanikwa chete kubva muropa remvura;hazvibviri kuwana PRP kubva muserum kana ropa rakavharwa.

Kune nzira dzakasiyana dzekutengeserana dzekuunganidza ropa uye kuwana PRP.Kusiyana pakati pavo kunosanganisira kuwanda kweropa rinoda kutorwa kubva kumurwere;isolation technique;centrifugation speed;chiyero chekuisa pfungwa pahuwandu mushure me centrifugation;nguva yekugadzirisa;

Nzira dzakasiyana-siyana dzekugadzirisa ropa dzakanzi dzinokanganisa chiyero cheleukocyte.Nhamba dzeplatelet mu1 μL yeropa kubva kuvanhu vane hutano dzinobva pa150,000 kusvika pa300,000.Platelets ndiwo ane basa rekumisa kubuda ropa.

Iwo alpha granules emaplatelet ane marudzi akasiyana emapuroteni akadai sekukura zvinhu (eg kushandura growth factor beta, insulin-like growth factor, epidermal growth factor), chemokines, coagulants, anticoagulants, fibrinolytic proteins, adhesion proteins, Integral membrane proteins, immune mediators. , angiogenic factors uye inhibitors, uye bactericidal mapuroteni.

Iyo chaiyo nzira yePRP chiito inoramba isingazivikanwi.PRP inoratidzika kuti inokurudzira chondrocytes kugadzirisa cartilage uye biosynthesis ye collagen uye proteoglycans.Yakashandiswa mumhando dzakasiyana dzekurapa dzakadai sekuvhiya nemuromo uye maxillofacial (kusanganisira temporomandibular OA), dermatology, ophthalmology, cardiothoracic kuvhiyiwa uye kuvhiyiwa kwepurasitiki.

 

(Zviri muchinyorwa ichi zvakadhindwa patsva, uye isu hatipe chero vimbiso yechokwadi, kuvimbika kana kuzara kwezviri muchinyorwa chino, uye hatina mhosva yemafungiro echinyorwa ichi, ndapota nzwisisa.)


Nguva yekutumira: Jul-27-2022