iphepha_ibhena

I-Molecular Mechanism kunye nokusebenza kakuhle kwePlatelet-Rich Plasma (PRP) Intra-articular Therapy

I-Primary knee osteoarthritis (OA) ihlala isisifo esingalawulekiyo esiyingozi.Ngokunyuka kwexesha lokuphila kunye nobhubhani wokutyeba, i-OA ibangela umthwalo okhulayo wezoqoqosho kunye nomzimba.I-Knee OA sisifo esinganyangekiyo se-musculoskeletal esinokuthi ekugqibeleni sifune ungenelelo lotyando.Ngoko ke, izigulane ziyaqhubeka nokukhangela unyango olunokuthi lube nonyango olungenalo utyando, njenge-injection ye-platelet-rich plasma (PRP) kwi-joint joint echaphazelekayo.

Ngokuka-Jayaram et al., i-PRP lunyango olusakhulayo lwe-OA.Nangona kunjalo, ubungqina beklinikhi bokusebenza kwayo busekho, kwaye indlela yokusebenza kwayo ayiqinisekanga.Nangona iziphumo ezithembisayo ziye zaxelwa malunga nokusetyenziswa kwe-PRP kwi-OA yamadolo, imibuzo ephambili efana nobungqina obuqinisekileyo malunga nokusebenza kwayo, iidosi ezisemgangathweni, kunye neendlela zokulungiselela ezilungileyo zihlala zingaziwa.

I-OA yamadolo iqikelelwa ukuba ichaphazela ngaphezu kwe-10% yabemi behlabathi, kunye nomngcipheko wobomi bonke obungama-45%.Izikhokelo zangoku zincoma zombini i-nonpharmacological (umzekelo, umthambo) kunye nonyango lwe-pharmacological, njenge-oral nonsteroidal anti-inflammatory drugs (NSAIDs).Nangona kunjalo, olu nyango ludla ngokuba neenzuzo zexesha elifutshane kuphela.Ngaphezu koko, ukusetyenziswa kweziyobisi kwizigulane ezine-comorbidities kulinganiselwe ngenxa yomngcipheko weengxaki.

I-corticosteroids ye-intra-articular idla ngokusetyenziswa kuphela kwiintlungu zexesha elifutshane ngenxa yokuba inzuzo yabo inqunyelwe kwiiveki ezimbalwa, kwaye i-injection ephindaphindiweyo ibonakaliswe ukuba idibene nokulahleka kwe-cartilage.Abanye ababhali bathi ukusetyenziswa kwe-hyaluronic acid (HA) kuyingxabano.Nangona kunjalo, abanye ababhali baxela ukukhululeka kwentlungu emva kwe-3 ukuya kwii-5 ii-injection zeveki ze-HA kwii-5 kwiiveki ze-13 (ngamanye amaxesha ukuya kwi-1 ngonyaka).

Xa ezinye iindlela ezingentla zingaphumeleli, i-knee arthroplasty (TKA) idla ngokucetyiswa njengonyango olusebenzayo.Nangona kunjalo, kuyabiza kwaye kunokubandakanya iziphumo ezibi zonyango kunye nasemva kokuhlinzwa.Ke ngoko, kubalulekile ukuchonga olunye unyango olukhuselekileyo nolusebenzayo lwe-OA yamadolo.

Unyango lwe-Biological, njenge-PRP, lusanda kuphandwa unyango lwe-knee OA.I-PRP yimveliso yegazi ye-autologous ene-concentration ephezulu yeeplatelet.Ukusebenza kwe-PRP kucatshangelwa ukuba kuhambelana nokukhululwa kwezinto zokukhula kunye nezinye iiamolekyu, kubandakanywa i-platelet-derived growth factor (PDGF), ukuguqula ukukhula kwe-TGF (TGF) -beta, i-insulin-like growth factor type I (IGF-I) , kunye ne-vascular endothelial growth factor (VEGF).

Iimpapasho ezininzi zibonisa ukuba i-PRP inokuthembisa unyango lwe-knee OA.Nangona kunjalo, uninzi aluvumelani ngeyona ndlela ilungileyo, kwaye kukho imida emininzi ethintela uhlalutyo olufanelekileyo lweziphumo zabo, emngciphekweni wokuthambekela.I-heterogeneity yamalungiselelo kunye neendlela zokutofa eziqeshwe kwizifundo ezixeliweyo kukulinganiselwa ekuchazeni inkqubo efanelekileyo ye-PRP.Ngaphaya koko, izilingo ezininzi zisebenzise i-HA njengomthelekisi, nto leyo eyimpikiswano ngokwayo.Ezinye izilingo zithelekisa i-PRP kunye ne-placebo kwaye zibonise ukuphuculwa kweempawu ezingcono kakhulu kune-saline kwi-6 kunye neenyanga ze-12.Nangona kunjalo, olu vavanyo luneziphene ezininzi zendlela, kubandakanya ukungabikho kokumfamekisa okufanelekileyo, okucebisa ukuba izibonelelo zabo zinokuthi ziqikelelwe.

Iingenelo ze-PRP kunyango lwe-OA yamadolo zimi ngolu hlobo lulandelayo: kulungele kakhulu ukusebenzisa ngenxa yokulungiselela ngokukhawuleza kunye nokuhlaselwa okuncinci;bubuchule obufikelelekayo ngenxa yokusetyenziswa kweziseko nezixhobo zenkonzo yezempilo karhulumente;kwaye kunokwenzeka ukuba ikhuseleke, kuba yimveliso ezenzekelayo.Ushicilelo lwangaphambili luchaze iingxaki ezincinci kunye nezexeshana.

Injongo yale nqaku kukuhlaziya indlela yokusebenza ye-molecular yangoku ye-PRP kunye nobungakanani bokusebenza kwe-intra-articular injection ye-PRP kwizigulane ezine-knee OA.

 

Indlela yemolekyuli yesenzo seplasma eneplatelet-rich

I-Cochrane Library kunye ne-PubMed (MEDLINE) ifuna izifundo ezinxulumene ne-PRI kwi-knee OA zahlaziywa.Ixesha lokukhangela lisusela ekuqaleni kwe-injini yokukhangela ukuya kwi-15 kaDisemba 2021. Izifundo kuphela ze-PRP kwi-knee OA ababhali abacinga ukuba banomdla kakhulu bafakiwe.I-PubMed ifumene amanqaku angama-454, apho i-80 ikhethiwe.Inqaku lifunyenwe kwiThala leencwadi laseCochrane, elikwafakwe kwisalathiso, elineembekiselo ezingama-80 zizonke.

Uphononongo olupapashwe kwi-2011 lubonise ukuba ukusetyenziswa kwezinto zokukhula (amalungu e-TGF-β superfamily, i-fibroblast growth factor family, i-IGF-I kunye ne-PDGF) ekulawuleni i-OA ibonakala ithembisa.

Kwi-2014, uSandman et al.ingxelo yokuba unyango lwe-PRP lwe-OA izicubu ezidibeneyo zibangele ukuhla kwe-catabolism;nangona kunjalo, i-PRP ibangele ukuhla okukhulu kwe-matrix metalloproteinase 13, ukwanda kwe-hyalurronan synthase i-2 ibonakaliso kwiiseli ze-synovial, kunye nokunyuka komsebenzi we-cartilage synthesis.Iziphumo zolu phononongo zibonisa ukuba i-PRP ivuselela ukuveliswa kwe-HA engapheliyo kwaye iyanciphisa i-cartilage catabolism.I-PRP iphinde ivimbele ukuxinwa kwabalamli abavuthayo kunye ne-gene expression kwi-synovial kunye ne-chondrocytes.

Kwi-2015, uphando lwebhubhoratri elawulwayo lubonise ukuba i-PRP ikhuthaze kakhulu ukwanda kweeseli kunye neprotheyini ye-surface secretion kwi-knee cartilage kunye neeseli ze-synovial.Olu qwalaselo lunceda ukucacisa iindlela ze-biochemical ezinxulumene nokusebenza kwe-PRP kunyango lwe-knee OA.

Kwimodeli ye-murine ye-OA (isifundo sebhubhoratri esilawulwayo) esichazwe nguKhatab et al.Kwi-2018, ii-injection ezininzi ze-PRP zokukhululwa zinciphisa intlungu kunye nobukhulu be-synovial, mhlawumbi i-mediated macrophage subtypes.Ke, ezi naliti zibonakala zinciphisa iintlungu kunye nokudumba kwe-synovial, kwaye zinokunqanda uphuhliso lwe-OA kwizigulana ezine-OA yangethuba.

Kwi-2018, ukuphononongwa kweencwadi ze-database ze-PubMed zagqiba ukuba unyango lwe-PRP lwe-OA lubonakala lusebenzisa i-modulating effect kwindlela ye-Wnt / β-catenin, enokubaluleka ekufezekiseni imiphumo yayo yeklinikhi enenzuzo.

Ngo-2019, uLiu et al.yaphanda indlela yeemolekyuli apho i-PRP-derived exosomes ibandakanyekayo ekunciphiseni i-OA.Kubalulekile ukugxininisa ukuba i-exosomes idlala indima ebalulekileyo kunxibelelwano lwe-intercellular.Kule sifundo, i-chondrocyte ye-rabbit yokuqala yahlukaniswa kwaye yaphathwa nge-interleukin (IL) -1β ukuseka i-in vitro model ye-OA.Ukunyuka, ukufuduka, kunye nokuhlolwa kwe-apoptosis kwalinganiswa kwaye kuthelekiswa phakathi kwe-PRP-derived exosomes kunye ne-PRP esebenzayo ukuvavanya umphumo wonyango kwi-OA.Iindlela ezibandakanyekayo kwindlela yokubonisa i-Wnt/β-catenin zaphandwa luhlalutyo lwe-blot yasentshona.I-PRP-derived exosomes ifunyenwe ibe nemiphumo efanayo okanye engcono yonyango kwi-OA kune-PRP esebenzayo kwi-vitro nakwi-vivo.

Kwimodeli yemouse ye-OA ye-posttraumatic echazwe kwi-2020, uJayaram et al.cebisa ukuba imiphumo ye-PRP kwi-OA yokuqhubela phambili kunye ne-hyperalgesia ebangelwa yizifo inokuthi ixhomekeke kwi-leukocyte.Kwakhona bakhankanya ukuba i-PRP ye-leukocyte-poor (LP-PRP) kunye nenani elincinci le-leukocyte-rich PRP (LR-PRP) likhusela umthamo kunye nokulahleka komhlaba.

Iziphumo ezichazwe nguYang et al.Uphononongo lwe-2021 lubonise ukuba i-PRP ubuncinane iyancipha i-IL-1β-induced chondrocyte apoptosis kunye nokuvuvukala ngokuthintela i-hypoxia-inducible factor 2α.

Kwimodeli yegundane ye-OA usebenzisa i-PRP, i-Sun et al.I-microRNA-337 kunye ne-microRNA-375 zifunyenwe ukulibazisa ukuqhubela phambili kwe-OA ngokuchaphazela ukuvuvukala kunye ne-apoptosis.

Ngokutsho kukaSheean et al., Imisebenzi ye-biological ye-PRP i-multifaceted: i-platelet alpha granules ikhuthaza ukukhululwa kwezinto ezahlukeneyo zokukhula, kuquka i-VEGF kunye ne-TGF-beta, kwaye ukuvuvukala kulawulwa ngokuvimbela i-nuclear factor-κB indlela.

Ukugxininiswa kwezinto ezihlekisayo kwi-PRP ezilungiselelwe kuzo zombini iikiti kunye nemiphumo ye-humoral factor kwi-macrophage phenotype zaphandwa.Bafumene umahluko kumacandelo eselula kunye ne-humoral factor concentrations phakathi kwe-PRP ehlanjululweyo kusetyenziswa iikiti ezimbini.I-autologous protein solution ikiti ye-LR-PRP inemilinganiselo ephezulu ye-M1 kunye ne-M2 enxulumene ne-macrophage.Ukongezwa kwe-PRP ephezulu kwi-culture medium ye-monocyte-derived macrophages kunye ne-M1 polarized macrophages ibonise ukuba i-PRP ivimbele i-M1 macrophage polarization kwaye ikhuthaze i-M2 macrophage polarization.

Kwi-2021, uSzwedowski et al.Izinto zokukhula ezikhutshwe kwi-OA yamadolo emva kwe-injection ye-PRP zichazwe: i-tumor necrosis factor (TNF), i-IGF-1, i-TGF, i-VEGF, i-disggregate, kunye ne-metalloproteinases ene-thrombospondin motifs, i-interleukins, i-matrix metalloproteinases, i-epidermal factor factor, ukukhula kwe-hepatocyte, i-fibroblast. ukukhula, ukukhula kwe-keratinocyte kunye ne-platelet factor 4.

1. IPDGF

I-PDGF yafunyanwa okokuqala kwiiplatelets.Iyakwazi ukumelana nobushushu, i-acid-resistant, i-cationic polypeptide eyenza i-hydrolyzed ngokulula yi-trypsin.Yenye yezinto zokuqala zokukhula ezivela kwiindawo zokwaphuka.Ibonakaliswa kakhulu kwiithambo ezibuhlungu, okwenza i-osteoblasts i-chemotactic kwaye yande, ikhulise amandla e-collagen synthesis, kwaye ikhuthaze ukuxutywa kwe-osteoclasts, ngaloo ndlela ikhuthaza ukubunjwa kwamathambo.Ukongeza, i-PDGF inokukhuthaza ukwanda kunye nokwahlulahlula i-fibroblasts kunye nokukhuthaza ukulungiswa kwezicubu.

2. TGF-B

I-TGF-B i-polypeptide eyenziwe ngamatyathanga e-2, esebenza kwi-fibroblasts kunye ne-pre-osteoblasts kwi-paracrine kunye / okanye ifom ye-autocrine, ivuselela ukwanda kwe-osteoblasts kunye ne-pre-osteoblasts kunye ne-synthesis ye-collagen fibers, njenge-chemokine, i-osteoprogenitor. iiseli zifakwe kwizicubu zamathambo ezenzakeleyo, kwaye ukubunjwa kunye nokufunxwa kwe-osteoclasts kuyanqandwa.I-TGF-B iphinda ilawule i-ECM (i-matrix ye-extracellular) synthesis, ineempembelelo ze-chemotactic kwi-neutrophils kunye ne-monocytes, kwaye idibanisa iimpendulo zendawo ezivuthayo.

3. VEGF

I-VEGF yi-dimeric glycoprotein, ebophelela kwi-receptors ebusweni beeseli ze-vascular endothelial ngokusebenzisa i-autocrine okanye i-paracrine, ikhuthaza ukwanda kweeseli ze-endothelial, ikhuthaza ukusekwa kunye nokusekwa kwemithambo yegazi emitsha, inikezela ngeoksijini kwiziphelo zokuphuka, ibonelela ngezondlo, kwaye ihambisa inkunkuma ye-metabolic. ., ukubonelela nge-microenvironment efanelekileyo kwi-metabolism kwindawo yokuvuselela amathambo wendawo.Emva koko, phantsi kwesenzo se-VEGF, umsebenzi we-alkaline phosphatase wokuhlukana kwe-osteoblast uphuculwe, kwaye iityuwa ze-calcium zendawo zifakwe ukukhuthaza ukuphulukiswa kwe-fracture.Ukongeza, i-VEGF ikhuthaza ukulungiswa kwezicubu ezithambileyo ngokuphucula ukuhanjiswa kwegazi kwezicubu ezithambileyo ezijikeleze ukwaphuka, kwaye ikhuthaza ukuphiliswa kokwaphuka, kwaye ibe nefuthe lokukhuthazana kunye nePDGF.

4. EGF

I-EGF yintlupheko yeseli enamandla ekhuthaza ulwahlulo kunye nokwanda kweentlobo ezahlukeneyo zeeseli zezicubu emzimbeni, ngelixa ikhuthaza ukuhlanganiswa kwe-matrix kunye nokubekwa, ukukhuthaza ukubunjwa kwezicubu ze-fibrous, kunye nokuqhubeka nokuguqula ithambo ukuze kuthathelwe indawo ukubunjwa kwezicubu zethambo.Enye into yokuba i-EGF ithatha inxaxheba ekulungiseni i-fracture kukuba inokusebenza i-phospholipase A, ngaloo ndlela ikhuthaza ukukhululwa kwe-arachidonic acid kwiiseli ze-epithelial, kunye nokukhuthaza ukuhlanganiswa kwe-prostaglandin ngokulawula imisebenzi ye-cyclooxygenase kunye ne-lipoxygenase.Indima ye-resorption kunye nokwakhiwa kwamathambo kamva.Ingabonwa ukuba i-EGF ithatha inxaxheba kwinkqubo yokuphulukisa i-fractures kwaye inokukhawulezisa ukuphulukiswa kwe-fracture.Ukongezelela, i-EGF inokukhuthaza ukwanda kweeseli ze-epidermal kunye neeseli ze-endothelial, kwaye zenze iiseli ze-endothelial zifudukele kwindawo yesilonda.

5. IGF

I-IGF-1 i-polypeptide ye-chain eyodwa ebophelela kwi-receptors emathanjeni kwaye isebenze i-tyrosine protease emva kwe-autophosphorylation ye-receptor, ekhuthaza i-phosphorylation ye-insulin receptor substrates, ngaloo ndlela ilawula ukukhula kweeseli, ukwanda kunye ne-metabolism.Iyakwazi ukuvuselela i-Osteoblasts kunye ne-pre-osteoblasts, ikhuthaze i-cartilage kunye nokwakheka kwe-matrix yamathambo.Ukongezelela, idlala indima ebalulekileyo ekudibaniseni ukuguqulwa kwamathambo ngokudibanisa ukuhlukana kunye nokwakhiwa kwe-osteoblasts kunye ne-osteoclasts kunye nemisebenzi yabo yokusebenza.Ukongeza, i-IGF yenye yezinto ezibalulekileyo ekulungiseni amanxeba.Yinto ekhuthaza ukungena kwe-fibroblasts kwi-cell cycle kwaye ivuselele ukuhlukana kunye nokuhlanganiswa kwe-fibroblasts.

 

I-PRP yi-autologous concentrate yeeplatelet kunye nezinto zokukhula ezivela kwi-centrifuged blood.Kukho ezinye iindidi ezimbini zeplatelet concentrates: iplatelet-rich fibrin kunye neplasma-rich growth factor.I-PRP inokufumaneka kuphela kwigazi elimanzi;akunakwenzeka ukufumana i-PRP kwi-serum okanye i-clot blood.

Kukho iindlela ezahlukeneyo zorhwebo zokuqokelela igazi kunye nokufumana i-PRP.Umahluko phakathi kwabo uquka umlinganiselo wegazi ekufuneka litsalwe kumguli;ubuchule bokuzihlukanisa;isantya se-centrifugation;ubungakanani bokugxila kumthamo emva kokumisa i-centrifugation;ixesha lokucubungula;

Iindlela ezahlukeneyo ze-centrifugation zegazi ziye zabikwa ukuba zichaphazela umlinganiselo we-leukocyte.Amanani eeplatelet kwi-1 μL yegazi kubantu abasempilweni aqala kwi-150,000 ukuya kuma-300,000.IiPlatelets zinoxanduva lokuyeka ukopha.

Iialpha granules zeplatelet zineentlobo ezahlukeneyo zeprotheyini ezifana nezinto ezikhula (umzekelo ukuguqula ukukhula kwebeta, i-insulin-like growth factor, epidermal growth factor), iichemokines, coagulants, anticoagulants, fibrinolytic proteins, adhesion proteins, Integral membrane proteins, immune mediators. , izinto ze-angiogenic kunye ne-inhibitors, kunye neeprotheni ze-bactericidal.

Indlela echanekileyo yesenzo se-PRP ayisaziwa.I-PRP ibonakala ivuselela i-chondrocytes ukulungisa i-cartilage kunye ne-biosynthesis ye-collagen kunye ne-proteoglycans.Isetyenziswe kwiingcali ezahlukeneyo zonyango ezifana notyando lomlomo kunye ne-maxillofacial (kubandakanya i-temporomandibular OA), i-dermatology, i-ophthalmology, utyando lwe-cardiothoracic kunye notyando lweplastiki.

 

(Imixholo yeli nqaku ishicilelwe, kwaye asiboneleli nasiphi na isiqinisekiso esicacileyo okanye esichaziweyo sokuchaneka, ukuthembeka okanye ukugqibelela kokuqulathwe kweli nqaku, kwaye abanaxanduva ngezimvo zeli nqaku, nceda uqonde.)


Ixesha lokuposa: Jul-27-2022