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Molecular Mechanism ndi Mphamvu ya Platelet-Rich Plasma (PRP) Intra-articular Therapy

Primary knee osteoarthritis (OA) imakhalabe matenda osachiritsika osachiritsika.Chifukwa cha kuchuluka kwa nthawi yoyembekezeka ya moyo komanso mliri wa kunenepa kwambiri, OA ikubweretsa zovuta zachuma komanso zakuthupi.Knee OA ndi matenda aakulu a minofu ndi mafupa omwe angafunike kuchitidwa opaleshoni.Choncho, odwala akupitirizabe kufunafuna mankhwala omwe angakhale osachita opaleshoni, monga jekeseni wa plasma wolemera kwambiri wa platelet (PRP) mu mgwirizano wa mawondo okhudzidwa.

Malinga ndi Jayaram et al., PRP ndi mankhwala omwe akubwera a OA.Komabe, umboni wachipatala wokhudza kugwira ntchito kwake ulibe, ndipo njira yake yochitira zinthu sizikudziwika.Ngakhale kuti zotsatira zodalirika zanenedwa ponena za kugwiritsa ntchito PRP mu OA ya bondo, mafunso ofunika kwambiri monga umboni wotsimikizirika wokhudzana ndi mphamvu zake, mlingo wokhazikika, ndi njira zokonzekera bwino sizidziwika.

Knee OA akuti ikhudza anthu opitilira 10% padziko lonse lapansi, ndipo chiwopsezo cha moyo wawo wonse ndi 45%.Malangizo amasiku ano amalimbikitsa onse osapharmacological (mwachitsanzo, masewera olimbitsa thupi) ndi mankhwala amankhwala, monga oral nonsteroidal anti-inflammatory drugs (NSAIDs).Komabe, mankhwala amenewa nthawi zambiri amakhala ndi ubwino wanthawi yochepa chabe.Komanso, kugwiritsa ntchito mankhwala kwa odwala omwe ali ndi comorbidities kumakhala kochepa chifukwa cha chiopsezo cha zovuta.

Intra-articular corticosteroids nthawi zambiri amagwiritsidwa ntchito pofuna kuchepetsa kupweteka kwa nthawi yochepa chifukwa phindu lawo ndilochepa kwa masabata angapo, ndipo jekeseni mobwerezabwereza yasonyezedwa kuti ikugwirizana ndi kuwonongeka kwa cartilage.Olemba ena amanena kuti kugwiritsa ntchito hyaluronic acid (HA) kumatsutsana.Komabe, olemba ena adanenanso kuti kupweteka kwapweteka pambuyo pa 3 kwa 5 jekeseni wa mlungu uliwonse wa HA kwa 5 kwa masabata a 13 (nthawi zina mpaka chaka cha 1).

Pamene njira zomwe zili pamwambazi zikulephera, mawondo amtundu wa arthroplasty (TKA) nthawi zambiri amalimbikitsidwa ngati mankhwala othandiza.Komabe, ndizokwera mtengo ndipo zingaphatikizepo zotsatira zoyipa zachipatala ndi pambuyo pa opaleshoni.Chifukwa chake, ndikofunikira kuzindikira njira zina zochiritsira zotetezeka komanso zogwira mtima za OA ya bondo.

Thandizo lachilengedwe, monga PRP, lafufuzidwa posachedwapa pofuna kuchiza mawondo OA.PRP ndi chinthu chamagazi cha autologous chokhala ndi mapulateleti ambiri.Kuchita bwino kwa PRP kumaganiziridwa kuti kumagwirizana ndi kutulutsidwa kwa zinthu za kukula ndi mamolekyu ena, kuphatikizapo platelet-derived growth factor (PDGF), transforming growth factor (TGF) -beta, insulin-like growth factor type I (IGF-I) ndi vascular endothelial growth factor (VEGF).

Zolemba zingapo zikuwonetsa kuti PRP ikhoza kulonjeza chithandizo cha mawondo OA.Komabe, ambiri sagwirizana pa njira yabwino kwambiri, ndipo pali zolepheretsa zambiri zomwe zimalepheretsa kusanthula koyenera kwa zotsatira zawo, pangozi ya kukondera.Kusiyanasiyana kwa njira zokonzekera ndi jekeseni zomwe zimagwiritsidwa ntchito muzofukufuku zomwe zafotokozedwa ndizolepheretsa kufotokozera dongosolo labwino la PRP.Kuphatikiza apo, mayesero ambiri adagwiritsa ntchito HA ngati wofananiza, zomwe zimatsutsana zokha.Mayesero ena adayerekeza PRP ndi placebo ndipo adawonetsa kusintha kwabwinoko kuposa saline pamiyezi 6 ndi 12.Komabe, mayeserowa ali ndi zolakwika zambiri zamakina, kuphatikizapo kusowa kwa khungu koyenera, kutanthauza kuti phindu lawo likhoza kuwerengedwa mopambanitsa.

Ubwino wa PRP pochiza ma OA a bondo ndi awa: ndizosavuta kugwiritsa ntchito chifukwa cha kukonzekera kwake mwachangu komanso kuwononga pang'ono;ndi njira yotsika mtengo chifukwa chogwiritsa ntchito zida ndi zida zomwe zilipo kale;ndipo zikutheka kukhala otetezeka, chifukwa ndi autologous mankhwala.Zofalitsa zam'mbuyomu zangonena zovuta zazing'ono komanso zosakhalitsa.

Cholinga cha nkhaniyi ndikuwonanso momwe PRP imagwirira ntchito komanso kuchuluka kwa jekeseni wa intra-articular wa PRP kwa odwala omwe ali ndi mawondo OA.

 

Molecular imagwirira ntchito ya plasma yokhala ndi mapulateleti

Library ya Cochrane ndi PubMed (MEDLINE) amafufuza maphunziro okhudzana ndi PRI mu knee OA adafufuzidwa.Nthawi yofufuzira ndi kuyambira pachiyambi cha injini yofufuzira mpaka December 15, 2021. Maphunziro okha a PRP mu OA ya bondo omwe olembawo amawaona kuti ndi ofunika kwambiri.PubMed idapeza zolemba za 454, zomwe 80 zidasankhidwa.Nkhani inapezedwa mu Laibulale ya Cochrane, yomwe ilinso ndi maumboni 80.

Kafukufuku wofalitsidwa mu 2011 adawonetsa kuti kugwiritsa ntchito zinthu zakukula (mamembala a TGF-β superfamily, fibroblast growth factor family, IGF-I ndi PDGF) poyang'anira OA akuwoneka ngati akulonjeza.

Mu 2014, Sandman et al.adanenanso kuti chithandizo cha PRP cha minofu ya OA chinachititsa kuchepa kwa catabolism;komabe, PRP inachititsa kuchepa kwakukulu kwa matrix metalloproteinase 13, kuwonjezeka kwa hyaluronan synthase 2 mawu m'maselo a synovial, ndi kuwonjezeka kwa ntchito ya kaphatikizidwe ka cartilage.Zotsatira za kafukufukuyu zikusonyeza kuti PRP imathandizira kupanga endogenous HA ndipo imachepetsa cartilage catabolism.PRP inalepheretsanso kuchuluka kwa oyimira pakati otupa komanso mawonekedwe awo a jini mu synovial ndi chondrocytes.

Mu 2015, kafukufuku wa labotale woyendetsedwa bwino adawonetsa kuti PRP idalimbikitsa kwambiri kuchuluka kwa maselo komanso kutulutsa mapuloteni amtundu wa mawondo amunthu ndi ma synovial cell.Zowonera izi zimathandizira kufotokozera njira zama biochemical zomwe zimagwirizanitsidwa ndi mphamvu ya PRP pochiza mawondo OA.

Mu chitsanzo cha murine OA (kafukufuku wa labotale yoyendetsedwa) yolembedwa ndi Khatab et al.Mu 2018, jakisoni wotulutsa PRP angapo adachepetsa ululu ndi makulidwe a synovial, mwina amayanjanitsidwa ndi ma macrophage subtypes.Choncho, jakisoniwa amawoneka kuti amachepetsa ululu ndi kutupa kwa synovial, ndipo akhoza kulepheretsa kukula kwa OA kwa odwala omwe ali ndi OA oyambirira.

Mu 2018, kuwunika kwa zolemba zamabuku a PubMed kunatsimikizira kuti chithandizo cha PRP cha OA chikuwoneka kuti chili ndi mphamvu yosinthira njira ya Wnt/β-catenin, yomwe ingakhale yofunikira kuti akwaniritse zotsatira zake zachipatala.

Mu 2019, Liu et al.adafufuza momwe ma molekyulu omwe amapangidwa ndi PRP-derived exosomes amathandizira kuchepetsa OA.Ndikofunikira kuwunikira kuti ma exosomes amagwira ntchito yofunika kwambiri pakulumikizana kwama cell.Mu phunziro ili, ma chondrocyte a kalulu oyambirira anali olekanitsidwa ndipo amathandizidwa ndi interleukin (IL) -1β kuti akhazikitse chitsanzo cha in vitro cha OA.Kuchulukitsa, kusamuka, ndi kuyesa kwa apoptosis kunayesedwa ndikuyerekeza pakati pa ma exosomes opangidwa ndi PRP ndi activated PRP kuti awone momwe achire pa OA.Njira zomwe zimakhudzidwa ndi njira yowonetsera Wnt / β-catenin zinafufuzidwa ndi kusanthula kwa kumadzulo kwa blot.Ma exosomes opangidwa ndi PRP adapezeka kuti ali ndi zotsatira zofanana kapena zabwinoko zochiritsira pa OA kuposa activated PRP in vitro and in vivo.

Mu mtundu wa mbewa wa posttraumatic OA yomwe idanenedwa mu 2020, Jayaram et al.zikuwonetsa kuti zotsatira za PRP pakukula kwa OA ndi hyperalgesia yomwe imayambitsa matenda ikhoza kukhala yodalira leukocyte.Iwo adanenanso kuti PRP (LP-PRP) ya leukocyte-poor (LP-PRP) ndi PRP (LR-PR) yochuluka ya leukocyte (LR-PR)) imalepheretsa kuchuluka kwa mphamvu ndi kuwonongeka kwa pamwamba.

Zomwe zapezedwa ndi Yang et al.Kafukufuku wa 2021 adawonetsa kuti PRP yocheperako pang'ono IL-1β-induced chondrocyte apoptosis ndi kutupa mwa kuletsa hypoxia-inducible factor 2α.

Muchitsanzo cha makoswe a OA pogwiritsa ntchito PRP, Sun et al.MicroRNA-337 ndi microRNA-375 adapezeka kuti akuchedwetsa kupita kwa OA pokhudza kutupa ndi apoptosis.

Malingana ndi Sheean et al., zochitika zamoyo za PRP ndizochuluka: mapulateleti a alpha granules amalimbikitsa kumasulidwa kwa zinthu zosiyanasiyana za kukula, kuphatikizapo VEGF ndi TGF-beta, ndipo kutupa kumayendetsedwa ndi kuletsa njira ya nyukiliya-κB.

Kukhazikika kwazinthu zoseketsa mu PRP zokonzedwa kuchokera ku zida zonse ziwiri ndi zotsatira za zinthu zoseketsa pa macrophage phenotype zidafufuzidwa.Iwo adapeza kusiyana kwa ma cell ndi kuchuluka kwa humoral factor pakati pa PRP yoyeretsedwa pogwiritsa ntchito zida ziwirizi.Pulogalamu ya autologous protein solution LR-PRP ili ndi zinthu zambiri zokhudzana ndi M1 ndi M2 macrophage.Kuwonjezera kwa PRP supernatant ku chikhalidwe cha chikhalidwe cha monocyte-derived macrophages ndi M1 polarized macrophages anasonyeza kuti PRP inaletsa M1 macrophage polarization ndikulimbikitsa M2 macrophage polarization.

Mu 2021, Szwedowski et al.Zinthu za kukula zomwe zimatulutsidwa m'magulu a mawondo a OA pambuyo pa jekeseni wa PRP amafotokozedwa: tumor necrosis factor (TNF), IGF-1, TGF, VEGF, disaggregate, ndi metalloproteinases ndi thrombospondin motifs, interleukins, matrix metalloproteinases, epidermal kukula factor, hepatocyte kukula, fibroblast factor. kukula, keratinocyte kukula factor ndi platelet factor 4.

1. PDGF

PDGF idapezeka koyamba m'mapulateleti.Ndiwopanda kutentha, wosamva asidi, cationic polypeptide yomwe imapangidwa mosavuta ndi trypsin.Ichi ndi chimodzi mwazinthu zoyamba kukula zomwe zimawonekera pamasamba ophwanyika.Iwo kwambiri anasonyeza zoopsa fupa minofu, zomwe zimapangitsa osteoblasts chemotactic ndi proliferates, kumawonjezera luso kolajeni kaphatikizidwe, ndi kulimbikitsa mayamwidwe osteoclasts, potero kulimbikitsa mafupa mapangidwe.Kuphatikiza apo, PDGF imathanso kulimbikitsa kufalikira ndi kusiyanitsa kwa fibroblasts ndikulimbikitsa kukonzanso minofu.

2. TGF-B

TGF-B ndi polypeptide yopangidwa ndi unyolo wa 2, womwe umagwira ntchito pa fibroblasts ndi pre-osteoblasts mu paracrine ndi / kapena mawonekedwe a autocrine, zomwe zimalimbikitsa kuchulukira kwa osteoblasts ndi pre-osteoblasts ndi kaphatikizidwe ka collagen fibers, monga chemokine, osteoprogenitor. maselo amatengeka mu minofu yovulalayo, ndipo mapangidwe ndi kuyamwa kwa osteoclasts amaletsedwa.TGF-B imayang'aniranso kaphatikizidwe ka ECM (extracellular matrix), imakhala ndi zotsatira za chemotactic pa neutrophils ndi monocytes, ndipo imayanjanitsa mayankho otupa am'deralo.

3. VEGF

VEGF ndi dimeric glycoprotein, yomwe imamangiriza ku zolandilira pamwamba pa ma cell a mtima endothelial kudzera pa autocrine kapena paracrine, imathandizira kufalikira kwa maselo a endothelial, imathandizira kupanga ndi kukhazikitsidwa kwa mitsempha yatsopano yamagazi, imapereka mpweya ku malekezero ophwanyika, imapereka michere, ndikunyamula zinyalala zama metabolic. ., kupereka microenvironment yabwino kwa kagayidwe kachakudya m'dera la kusinthika kwa mafupa.Kenako, pansi pa zochita za VEGF, ntchito ya alkaline phosphatase ya kusiyanitsa kwa osteoblast imakulitsidwa, ndipo mchere wa calcium wam'deralo umayikidwa kuti uchiritse kuchira.Kuphatikiza apo, VEGF imalimbikitsa kukonzanso minofu yofewa mwa kukonza magazi a minofu yofewa mozungulira fracture, ndikulimbikitsa machiritso a fracture, ndipo imakhala ndi mgwirizano wolimbikitsana ndi PDGF.

4. EGF

EGF ndi gawo lamphamvu la cell lomwe limalimbikitsa kugawikana ndi kufalikira kwa mitundu yosiyanasiyana ya maselo amthupi m'thupi, pomwe kulimbikitsa kaphatikizidwe ka matrix ndi kuyika, kulimbikitsa mapangidwe a minofu yamafuta, ndikupitiliza kusinthika kukhala fupa kuti m'malo mwa mafupa apangidwe.Chinthu chinanso chomwe EGF imatenga nawo gawo pakukonza fracture ndikuti imatha kuyambitsa phospholipase A, potero kulimbikitsa kutulutsidwa kwa arachidonic acid kuchokera ku maselo a epithelial, ndikulimbikitsa kaphatikizidwe ka prostaglandins mwa kuwongolera ntchito za cyclooxygenase ndi lipoxygenase.Udindo wa resorption ndipo kenako mapangidwe mafupa.Zitha kuwoneka kuti EGF imatenga nawo gawo pakuchiritsa kwa fractures ndipo imatha kufulumizitsa machiritso a fracture.Kuphatikiza apo, EGF imatha kulimbikitsa kuchuluka kwa ma cell a epidermal ndi ma cell endothelial, ndikupangitsa kuti maselo a endothelial asamukire kumtunda wa bala.

5. IGF

IGF-1 ndi polypeptide yamtundu umodzi yomwe imamangiriza ku zolandilira m'mafupa ndikuyambitsa tyrosine protease pambuyo pa receptor autophosphorylation, yomwe imalimbikitsa phosphorylation ya insulin receptor substrates, potero imayang'anira kukula kwa maselo, kuchulukana ndi metabolism.Ikhoza kulimbikitsa ma Osteoblasts ndi pre-osteoblasts, kulimbikitsa cartilage ndi mapangidwe a mafupa.Kuonjezera apo, zimagwira ntchito yofunikira pakugwirizanitsa kukonzanso mafupa mwa kugwirizanitsa kusiyanitsa ndi kupanga ma osteoblasts ndi osteoclasts ndi ntchito zawo zogwira ntchito.Kuphatikiza apo, IGF ndi imodzi mwazinthu zofunika pakukonza mabala.Ndi chinthu chomwe chimalimbikitsa kulowa kwa fibroblasts mu cell cycle ndikulimbikitsa kusiyanitsa ndi kaphatikizidwe ka fibroblasts.

 

PRP ndi autologous concentrate ya mapulateleti ndi kukula kwa zinthu zomwe zimachokera ku magazi a centrifuged.Pali mitundu ina iwiri ya mapulateleti omwe amakhazikika: mapulateleti olemera fibrin ndi plasma-rich growth factor.PRP ingapezeke kuchokera ku magazi amadzimadzi;sizingatheke kupeza PRP kuchokera ku seramu kapena magazi oundana.

Pali njira zosiyanasiyana zamalonda zopezera magazi ndikupeza PRP.Kusiyana pakati pawo kumaphatikizapo kuchuluka kwa magazi omwe amayenera kutengedwa kuchokera kwa wodwalayo;njira yodzipatula;liwiro la centrifugation;kuchuluka kwa kuyika voliyumu pambuyo pa centrifugation;processing nthawi;

Njira zosiyanasiyana za centrifugation mwazi zanenedwa kuti zimakhudza chiŵerengero cha leukocyte.Manambala a platelet mu 1 μL ya magazi a anthu athanzi amayambira 150,000 mpaka 300,000.Mapulateleti ali ndi udindo woletsa magazi.

Ma alpha granules a mapulateleti ali ndi mitundu yosiyanasiyana ya mapuloteni monga kukula kwa beta, insulin-like growth factor, epidermal growth factor, chemokines, coagulants, anticoagulants, ma fibrinolytic protein, adhesion proteins, Integral membrane proteins, immune mediators. , angiogenic factor ndi inhibitors, ndi mapuloteni a bactericidal.

Njira yeniyeni ya PRP sichidziwika.PRP ikuwoneka kuti imalimbikitsa chondrocytes kuti akonzenso chichereŵechereŵe ndi biosynthesis ya collagen ndi proteoglycans.Zakhala zikugwiritsidwa ntchito pazachipatala zosiyanasiyana monga opaleshoni yapakamwa ndi maxillofacial (kuphatikizapo temporomandibular OA), dermatology, ophthalmology, opaleshoni ya mtima ndi opaleshoni yapulasitiki.

 

(Zomwe zili m'nkhaniyi zidasindikizidwanso, ndipo sitikupereka chitsimikizo chotsimikizika kapena chotsimikizika pakulondola, kudalirika kapena kukwanira kwa zomwe zili m'nkhaniyi, ndipo sitili ndi udindo pamalingaliro ankhaniyi, chonde mvetsetsani.)


Nthawi yotumiza: Jul-27-2022