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Molecular Mechanism thiab Kev Ua Tau Zoo ntawm Platelet-Rich Plasma (PRP) Kev Kho Mob Intra-articular

Primary hauv caug osteoarthritis (OA) tseem yog tus kab mob degenerative uas tswj tsis tau.Nrog rau kev ua neej nyob nce ntxiv thiab kev rog rog, OA ua rau muaj kev lag luam thiab lub cev hnyav zuj zus.Lub hauv caug OA yog ib tus kab mob musculoskeletal ntev uas yuav tsum tau muaj kev phais.Yog li, cov neeg mob tseem tshawb nrhiav cov kev kho mob uas tsis yog phais, xws li txhaj tshuaj platelet-nplua nuj plasma (PRP) rau hauv lub hauv caug cuam tshuam.

Raws li Jayaram li al., PRP yog ib qho kev kho mob tshiab rau OA.Txawm li cas los xij, cov pov thawj kho mob ntawm nws cov txiaj ntsig tseem tsis muaj, thiab nws cov txheej txheem ntawm kev ua haujlwm tsis paub meej.Txawm hais tias cov txiaj ntsig tau txais txiaj ntsig tau tshaj tawm txog kev siv PRP hauv lub hauv caug OA, cov lus nug tseem ceeb xws li cov pov thawj pom tseeb txog nws cov txiaj ntsig, cov koob tshuaj, thiab cov tswv yim npaj zoo tseem tsis paub.

Lub hauv caug OA kwv yees yuav cuam tshuam ntau dua 10% ntawm cov pej xeem hauv ntiaj teb, nrog rau kev pheej hmoo ntawm lub neej ntawm 45%.Cov txheej txheem niaj hnub no pom zoo rau ob qho tib si tsis yog tshuaj kho mob (xws li, kev tawm dag zog) thiab kev kho tshuaj kho mob, xws li tshuaj tiv thaiv kab mob hauv qhov ncauj (NSAIDs).Txawm li cas los xij, cov kev kho mob no feem ntau tsuas muaj cov txiaj ntsig luv luv xwb.Tsis tas li ntawd, kev siv yeeb tshuaj hauv cov neeg mob uas muaj kev sib xyaw ua ke yog txwv vim muaj kev pheej hmoo ntawm cov teeb meem.

Intra-articular corticosteroids feem ntau tsuas yog siv rau kev kho mob luv luv vim tias lawv cov txiaj ntsig tau txwv rau ob peb lub lis piam, thiab kev txhaj tshuaj rov qab tau pom tias muaj feem cuam tshuam nrog cov pob txha mos ntau ntxiv.Qee tus kws sau ntawv hais tias kev siv hyaluronic acid (HA) yog qhov tsis sib haum xeeb.Txawm li cas los xij, lwm tus kws sau ntawv tau tshaj tawm qhov mob nyem tom qab 3 txog 5 lub lis piam txhaj tshuaj HA rau 5 txog 13 lub lis piam (qee zaum txog 1 xyoos).

Thaum cov kev xaiv saum toj no ua tsis tiav, tag nrho lub hauv caug arthroplasty (TKA) feem ntau pom zoo ua kev kho mob zoo.Txawm li cas los xij, nws kim heev thiab tuaj yeem cuam tshuam txog kev kho mob thiab tom qab kev phais mob.Yog li, nws yog ib qho tseem ceeb los txheeb xyuas lwm txoj kev nyab xeeb thiab kev kho mob zoo rau lub hauv caug OA.

Cov kev kho mob lom neeg, xws li PRP, tsis ntev los no tau tshawb fawb txog kev kho mob hauv caug OA.PRP yog cov khoom siv ntshav autologous nrog cov ntshav platelets siab.Kev ua tau zoo ntawm PRP yog xav tias muaj feem cuam tshuam nrog kev tso tawm ntawm cov khoom loj hlob thiab lwm cov molecules, suav nrog platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, insulin-like growth factor type I (IGF-I) , thiab vascular endothelial kev loj hlob factor (VEGF).

Ntau qhov kev tshaj tawm qhia tias PRP tuaj yeem cog lus rau kev kho mob hauv caug OA.Txawm li cas los xij, feem ntau tsis pom zoo rau txoj hauv kev zoo tshaj plaws, thiab muaj ntau yam kev txwv uas txwv tsis pub txheeb xyuas lawv cov txiaj ntsig, muaj kev pheej hmoo ntawm kev tsis ncaj ncees.Lub heterogeneity ntawm kev npaj thiab kev txhaj tshuaj ua haujlwm nyob rau hauv cov kev tshawb fawb qhia yog ib qho kev txwv nyob rau hauv kev txhais ib tug zoo tagnrho PRP system.Tsis tas li ntawd, feem ntau kev sim siv HA ua tus piv, uas yog qhov tsis sib haum xeeb hauv nws tus kheej.Qee qhov kev sim piv rau PRP rau cov placebo thiab pom tau tias muaj kev txhim kho cov tsos mob zoo dua li ntsev ntawm 6 thiab 12 lub hlis.Txawm li cas los xij, cov kev sim no muaj ntau yam kev tsis zoo, suav nrog qhov tsis muaj qhov muag tsis pom kev, qhia tias lawv cov txiaj ntsig yuav raug kwv yees ntau dhau.

Qhov zoo ntawm PRP rau kev kho mob ntawm lub hauv caug OA yog raws li hauv qab no: nws yog qhov yooj yim heev rau siv vim nws txoj kev npaj sai thiab kev tawm tsam tsawg;nws yog cov txheej txheem pheej yig vim yog siv cov qauv kev pabcuam kev noj qab haus huv rau pej xeem thiab khoom siv uas twb muaj lawm;thiab nws zoo li yuav muaj kev nyab xeeb, vim nws yog cov khoom siv autologous.Cov ntawv tshaj tawm dhau los tau tshaj tawm tsuas yog muaj teeb meem me me thiab ib ntus xwb.

Lub hom phiaj ntawm tsab xov xwm no yog los tshuaj xyuas cov txheej txheem molecular ntawm kev ua ntawm PRP thiab qhov ua tau zoo ntawm kev txhaj tshuaj intra-articular ntawm PRP hauv cov neeg mob hauv caug OA.

 

Molecular mechanism ntawm kev ua ntawm platelet-nplua nuj plasma

Lub Tsev Qiv Ntawv Cochrane thiab PubMed (MEDLINE) tshawb nrhiav PRI-txog kev tshawb fawb hauv lub hauv caug OA tau txheeb xyuas.Lub sijhawm tshawb nrhiav yog txij thaum pib ntawm lub tshuab tshawb nrhiav mus txog Lub Kaum Ob Hlis 15, 2021. Tsuas yog cov kev tshawb fawb ntawm PRP hauv caug OA uas cov kws sau ntawv suav tias yog qhov txaus siab tshaj plaws tau suav nrog.PubMed pom 454 kab lus, ntawm 80 raug xaiv.Ib tsab xov xwm tau pom nyob rau hauv Lub Tsev Qiv Ntawv Cochrane, uas tseem tau txheeb xyuas, nrog rau tag nrho ntawm 80 cov lus qhia.

Ib txoj kev tshawb fawb luam tawm xyoo 2011 tau qhia tias kev siv cov khoom loj hlob (cov tswv cuab ntawm TGF-β superfamily, fibroblast loj hlob yam tsev neeg, IGF-I thiab PDGF) hauv kev tswj hwm ntawm OA zoo li cog lus.

Xyoo 2014, Sandman et al.qhia tias kev kho PRP ntawm OA cov ntaub so ntswg ua rau txo qis hauv catabolism;Txawm li cas los xij, PRP ua rau muaj qhov txo qis hauv matrix metalloproteinase 13, nce hauv hyaluronan synthase 2 qhia hauv cov hlwb synovial, thiab nce hauv pob txha pob txha synthesis.Cov txiaj ntsig ntawm txoj kev tshawb no qhia tias PRP txhawb kev tsim cov endogenous HA thiab txo cov pob txha mos catabolism.PRP kuj inhibited qhov concentration ntawm inflammatory mediators thiab lawv cov noob qhia nyob rau hauv synovial thiab chondrocytes.

Hauv xyoo 2015, txoj kev tshawb fawb soj ntsuam tau pom tias PRP tau txhawb nqa cell proliferation thiab deg protein secretion nyob rau hauv tib neeg lub hauv caug pob txha mos thiab synovial hlwb.Cov kev soj ntsuam no pab piav qhia txog biochemical mechanisms cuam tshuam nrog kev ua tau zoo ntawm PRP hauv kev kho mob hauv caug OA.

Nyob rau hauv ib tug murine OA qauv (tswj soj ntsuam kuaj) qhia los ntawm Khatab li al.Hauv xyoo 2018, ntau qhov kev txhaj tshuaj PRP txo qis qhov mob thiab cov tuab tuab, tuaj yeem kho los ntawm macrophage subtypes.Yog li, cov tshuaj no tshwm sim los txo qhov mob thiab mob synovial, thiab tuaj yeem cuam tshuam OA kev loj hlob hauv cov neeg mob uas muaj OA thaum ntxov.

Hauv xyoo 2018, kev tshuaj xyuas ntawm PubMed cov ntaub ntawv sau tseg tau xaus lus tias kev kho PRP ntawm OA zoo li ua rau muaj kev hloov pauv ntawm txoj hauv kev Wnt / β-catenin, uas yuav yog qhov tseem ceeb rau kev ua tiav nws cov txiaj ntsig kho mob.

Xyoo 2019, Liu et al.tshawb xyuas cov txheej txheem molecular uas PRP-derived exosomes koom nrog hauv kev txo OA.Nws yog ib qho tseem ceeb kom nco ntsoov tias exosomes ua lub luag haujlwm tseem ceeb hauv kev sib txuas lus ntawm tes.Hauv txoj kev tshawb no, thawj tus luav chondrocytes raug cais thiab kho nrog interleukin (IL)-1β los tsim ib qho qauv hauv vitro ntawm OA.Kev loj hlob, kev tsiv teb tsaws, thiab kev soj ntsuam apoptosis tau ntsuas thiab piv ntawm PRP-derived exosomes thiab qhib PRP los ntsuas qhov kev kho mob ntawm OA.Cov txheej txheem koom nrog hauv Wnt / β-catenin signaling txoj kev tau tshawb xyuas los ntawm kev txheeb xyuas sab hnub poob.PRP-derived exosomes tau pom tias muaj qhov zoo sib xws lossis zoo dua kev kho mob ntawm OA dua li qhib PRP hauv vitro thiab hauv vivo.

Hauv tus qauv nas ntawm posttraumatic OA tshaj tawm hauv 2020, Jayaram li al.qhia tias qhov cuam tshuam ntawm PRP ntawm OA kev loj hlob thiab kab mob tshwm sim hyperalgesia tuaj yeem yog leukocyte-dependent.Lawv kuj tau hais tias leukocyte-poor PRP (LP-PRP) thiab ib qho me me ntawm leukocyte-nplua nuj PRP (LR-PRP) tiv thaiv qhov ntim thiab qhov poob.

Cov kev tshawb pom qhia los ntawm Yang et al.Txoj kev tshawb fawb 2021 tau pom tias PRP tsawg kawg ib nrab txo qis IL-1β-induced chondrocyte apoptosis thiab o los ntawm inhibiting hypoxia-inducible factor 2α.

Hauv cov qauv nas ntawm OA siv PRP, Sun et al.microRNA-337 thiab microRNA-375 tau pom tias ncua sijhawm OA kev loj hlob los ntawm kev cuam tshuam o thiab apoptosis.

Raws li Sheean li al., cov kev ua si lom neeg ntawm PRP muaj ntau yam: platelet alpha granules txhawb kev tso tawm ntawm ntau yam kev loj hlob, suav nrog VEGF thiab TGF-beta, thiab o yog tswj los ntawm inhibiting nuclear factor-κB txoj hauv kev.

Cov ntsiab lus ntawm kev lom zem hauv PRP tau npaj los ntawm ob qho khoom siv thiab qhov cuam tshuam ntawm kev lom zem ntawm macrophage phenotype tau tshawb xyuas.Lawv pom qhov sib txawv ntawm cov khoom siv ntawm tes thiab kev lom zem ntau ntawm PRP purified siv ob cov khoom siv.Cov khoom siv autologous protein tov LR-PRP muaj ntau dua ntawm M1 thiab M2 macrophage ntsig txog yam.Ntxiv ntawm PRP supernatant rau kab lis kev cai nruab nrab ntawm monocyte-derived macrophages thiab M1 polarized macrophages qhia tias PRP inhibited M1 macrophage polarization thiab txhawb M2 macrophage polarization.

Xyoo 2021, Szwedowski et al.Kev loj hlob ntawm OA pob qij txha tom qab PRP txhaj tshuaj tau piav qhia: qog necrosis factor (TNF), IGF-1, TGF, VEGF, disaggregate, thiab metalloproteinases nrog thrombospondin motifs, interleukins, matrix metalloproteinases, epidermal growth factor, hepatocyte kev loj hlob, Kev loj hlob zoo, keratinocyte kev loj hlob zoo thiab platelet factor 4.

1. PDGF

PDGF tau pom thawj zaug hauv platelets.Nws yog qhov kub-resistant, acid-resistant, cationic polypeptide uas yooj yim hydrolyzed los ntawm trypsin.Nws yog ib qho ntawm cov kev loj hlob ntxov tshaj plaws uas tshwm sim hauv cov chaw tawg.Nws yog heev nthuav nyob rau hauv cov pob txha raug mob, uas ua rau osteoblasts chemotactic thiab proliferates, tsub kom lub peev xwm ntawm collagen synthesis, thiab txhawb kev nqus ntawm osteoclasts, yog li txhawb cov pob txha tsim.Tsis tas li ntawd, PDGF tseem tuaj yeem txhawb nqa kev loj hlob thiab kev sib txawv ntawm fibroblasts thiab txhawb kev kho cov ntaub so ntswg.

2. TGF-B

TGF-B yog polypeptide tsim los ntawm 2 chains, uas ua rau fibroblasts thiab pre-osteoblasts nyob rau hauv ib tug paracrine thiab / los yog autocrine daim ntawv, stimulating proliferation ntawm osteoblasts thiab pre-osteoblasts thiab synthesis ntawm collagen fibers, raws li ib tug chemokine, lub osteoprogenitor. cov hlwb tau nqus mus rau hauv cov pob txha raug mob, thiab kev tsim thiab nqus ntawm osteoclasts yog inhibited.TGF-B kuj tswj ECM (extracellular matrix) synthesis, muaj chemotactic teebmeem ntawm neutrophils thiab monocytes, thiab kho cov lus teb inflammatory hauv zos.

3. VEGF

VEGF yog dimeric glycoprotein, uas khi rau receptors nyob rau saum npoo ntawm vascular endothelial hlwb los ntawm autocrine los yog paracrine, txhawb endothelial cell proliferation, induces tsim thiab tsim cov hlab ntsha tshiab, muab cov pa oxygen rau pob txha xaus, muab cov as-ham, thiab thauj cov metabolic pov tseg. ., muab ib tug zoo microenvironment rau cov metabolism hauv lub zos pob txha regeneration cheeb tsam.Tom qab ntawd, nyob rau hauv qhov kev txiav txim ntawm VEGF, alkaline phosphatase kev ua ntawm osteoblast sib txawv yog txhim kho, thiab cov calcium ntsev hauv zos tau tso los txhawb kev puas tsuaj.Tsis tas li ntawd, VEGF txhawb kev kho cov ntaub so ntswg los ntawm kev txhim kho cov ntshav ntawm cov nqaij mos nyob ib ncig ntawm lub pob txha, thiab txhawb kev kho cov pob txha, thiab muaj kev sib koom ua ke nrog PDGF.

4. EGF

EGF yog lub zog faib ntawm tes txhawb nqa qhov tseem ceeb uas txhawb nqa kev faib thiab kev loj hlob ntawm ntau hom ntaub so ntswg hauv lub cev, thaum txhawb nqa matrix synthesis thiab deposition, txhawb kev tsim cov ntaub so ntswg, thiab txuas ntxiv hloov mus rau hauv pob txha los hloov cov pob txha tsim.Lwm qhov tseem ceeb uas EGF koom nrog kev kho pob txha yog tias nws tuaj yeem qhib phospholipase A, yog li txhawb kev tso tawm ntawm arachidonic acid los ntawm cov hlwb epithelial, thiab txhawb cov synthesis ntawm prostaglandins los ntawm kev tswj cov dej num ntawm cyclooxygenase thiab lipoxygenase.Lub luag haujlwm ntawm resorption thiab tom qab tsim cov pob txha.Nws tuaj yeem pom tau tias EGF koom nrog cov txheej txheem kho cov pob txha thiab tuaj yeem ua kom cov pob txha zoo.Tsis tas li ntawd, EGF tuaj yeem txhawb kev loj hlob ntawm cov hlwb epidermal thiab endothelial hlwb, thiab ua rau cov hlwb endothelial tsiv mus rau qhov txhab.

5. IGF

IGF-1 yog ib leeg-chain polypeptide uas khi rau receptors hauv pob txha thiab ua kom tyrosine protease tom qab receptor autophosphorylation, uas txhawb nqa cov phosphorylation ntawm insulin receptor substrates, yog li tswj kev loj hlob ntawm tes, proliferation thiab metabolism.Nws tuaj yeem txhawb nqa Osteoblasts thiab pre-osteoblasts, txhawb cov pob txha mos thiab pob txha matrix tsim.Tsis tas li ntawd, nws ua lub luag haujlwm tseem ceeb hauv kev sib txuas ntawm cov pob txha hloov kho los ntawm kev sib kho qhov sib txawv thiab tsim cov osteoblasts thiab osteoclasts thiab lawv cov dej num ua haujlwm.Tsis tas li ntawd, IGF kuj yog ib qho tseem ceeb hauv kev kho qhov txhab.Nws yog ib qho tseem ceeb uas txhawb kev nkag mus ntawm fibroblasts rau hauv lub voj voog ntawm tes thiab txhawb kev sib txawv thiab kev sib txuas ntawm fibroblasts.

 

PRP yog ib qho autologous concentrate ntawm platelets thiab loj hlob yam uas tau los ntawm cov ntshav centrifuged.Muaj ob hom platelet concentrates: platelet-nplua nuj fibrin thiab plasma-nplua nuj loj hlob yam.PRP tsuas tuaj yeem tau los ntawm cov ntshav ua kua;Nws tsis tuaj yeem tau txais PRP los ntawm cov ntshav los yog cov ntshav txhaws.

Muaj ntau hom kev lag luam sib txawv los sau cov ntshav thiab tau txais PRP.Qhov sib txawv ntawm lawv suav nrog cov ntshav uas yuav tsum tau kos los ntawm tus neeg mob;txheej txheem cais;centrifugation ceev;tus nqi rau concentrate ntim tom qab centrifugation;lub sijhawm ua haujlwm;

Cov txheej txheem sib txawv ntawm cov ntshav centrifugation tau tshaj tawm los cuam tshuam rau leukocyte ratio.Platelet tooj nyob rau hauv 1 μL ntawm cov ntshav los ntawm cov neeg noj qab haus huv muaj li ntawm 150,000 txog 300,000.Platelets yog lub luag haujlwm rau kev tso ntshav.

Cov alpha granules ntawm platelets muaj ntau hom proteins xws li kev loj hlob yam tseem ceeb (xws li kev hloov pauv kev loj hlob beta, insulin zoo li kev loj hlob zoo, epidermal kev loj hlob), chemokines, coagulants, anticoagulants, fibrinolytic proteins, adhesion proteins, Integral membrane proteins, immune mediators. , angiogenic yam thiab inhibitors, thiab bactericidal proteins.

Qhov tseeb mechanism ntawm PRP kev txiav txim tseem tsis paub.PRP zoo li txhawb chondrocytes los kho pob txha mos thiab biosynthesis ntawm collagen thiab proteoglycans.Nws tau siv ntau yam kev kho mob tshwj xeeb xws li kev phais qhov ncauj thiab maxillofacial (xws li temporomandibular OA), dermatology, ophthalmology, phais mob plawv thiab phais yas.

 

(Cov ntsiab lus ntawm tsab xov xwm no tau luam tawm dua, thiab peb tsis muab ib qho kev qhia lossis kev lees paub rau qhov raug, kev ntseeg tau lossis ua tiav ntawm cov ntsiab lus muaj nyob rau hauv tsab xov xwm no, thiab tsis muaj lub luag haujlwm rau cov kev xav ntawm tsab xov xwm no, thov nkag siab.)


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