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Mechanism of Platelet Rich Plasma (PRP) Therapy Yolimbikitsa Machiritso a Tissue

Masiku ano, lingaliro lodziwika kuti PRP lidawonekera koyamba mu gawo la hematology m'ma 1970.Hematologists adapanga mawu akuti PRP zaka makumi angapo zapitazo kuti afotokoze plasma yomwe imachokera ku mapulateleti apamwamba kuposa mtengo woyambira wamagazi am'magazi.Zaka zoposa khumi pambuyo pake, PRP idagwiritsidwa ntchito pa opaleshoni ya maxillofacial ngati mawonekedwe a platelet rich fibrin (PRF).Zomwe zili mu fibrin muzochokera ku PRP zili ndi phindu lofunika kwambiri chifukwa cha kumamatira kwake ndi makhalidwe osasunthika, pamene PRP yakhala ndi zotsutsana ndi zotupa ndipo imapangitsa kuti maselo azichulukana.Pomaliza, cha m'ma 1990, PRP idayamba kutchuka.Pomalizira pake, luso limeneli linasamutsidwa ku madera ena azachipatala.Kuyambira nthawi imeneyo, mtundu uwu wa biology wabwino wakhala ukuphunziridwa kwambiri ndikugwiritsidwa ntchito pochiza kuvulala kosiyanasiyana kwa minofu ndi mafupa a akatswiri othamanga, zomwe zinalimbikitsanso chidwi chake m'ma TV.Kuphatikiza pa kukhala othandiza pamankhwala a mafupa ndi masewera, PRP imagwiritsidwanso ntchito mu ophthalmology, gynecology, urology ndi cardiology, ana ndi opaleshoni ya pulasitiki.M'zaka zaposachedwapa, PRP yayamikiridwanso ndi dermatologists chifukwa cha kuthekera kwake pochiza zilonda zapakhungu, kukonza zipsera, kusinthika kwa minofu, kubwezeretsa khungu komanso ngakhale tsitsi.

PRP

Poganizira kuti PRP ikhoza kuwongolera mwachindunji machiritso ndi njira zotupa, ndikofunikira kuwonetsa machiritso a machiritso ngati chofotokozera.Njira yochiritsira imagawidwa m'magawo anayi otsatirawa: hemostasis;Kutupa;Kuchulukitsa kwa ma cell ndi matrix, ndipo pamapeto pake kukonzanso mabala.

 

Machiritso a Minofu

Machiritso a machiritso a minofu amayambitsidwa, zomwe zimatsogolera kumagulu a mapulateleti Kupanga kwa magazi ndi chitukuko cha temporary extracellular matrix (ECM).Kenako, mapulateleti amamatira ku collagen yowonekera ndi ECM mapuloteni, zomwe zimayambitsa kutulutsidwa kwa mamolekyu a bioactive omwe amapezeka mu-granules.Mapulateleti ali ndi mamolekyu osiyanasiyana a bioactive, kuphatikizapo kukula, chemotherapy factor ndi cytokines, komanso proinflammatory mediators, monga prostaglandin, prostate cyclin, histamine, thromboxane, serotonin ndi bradykinin.

Gawo lomaliza la kuchira limadalira kukonzanso kwa bala.Kukonzanso minofu kumayendetsedwa mosamalitsa kuti pakhale mgwirizano pakati pa anabolic ndi machitidwe a catabolic.Panthawiyi, kukula kwa platelet-derived growth factor (PDGF) ndi kusintha kwa kukula (TGF- β) Fibronectin ndi fibronectin zimalimbikitsa kufalikira ndi kusamuka kwa fibroblasts, komanso kaphatikizidwe ka zigawo za ECM.Komabe, nthawi ya kukula kwa bala kumadalira kwambiri kuopsa kwa bala, makhalidwe a munthu payekha komanso mphamvu ya machiritso a minofu yovulalayo.Zinthu zina za pathophysiological ndi metabolism zimatha kukhudza machiritso, monga ischemia ya minofu, hypoxia, matenda, kusalinganika kwa kukula, komanso matenda okhudzana ndi metabolic syndrome.

The proinflammatory microenvironment imasokoneza machiritso.Chovuta kwambiri ndichakuti ntchito yayikulu ya proteinase imalepheretsa zochitika zachilengedwe za kukula kwa chinthu (GF).Kuphatikiza pa mitotic, angiogenic ndi chemotactic properties, PRP imakhalanso gwero lazinthu zambiri zakukula.Ma biomolecules awa amatha kuthana ndi zovuta zomwe zimachitika m'matenda otupa poletsa kutupa komanso kukhazikitsa zolimbikitsa za anabolic.Poganizira makhalidwe amenewa, ofufuza angapeze mwayi waukulu wochiza kuvulala kosiyanasiyana.

Matenda ambiri, makamaka amtundu wa minofu ndi mafupa, amadalira kwambiri zinthu zamoyo zomwe zimayendetsa njira yotupa, monga PRP pofuna kuchiza osteoarthritis.Pankhaniyi, thanzi la articular cartilage zimadalira kulondola kwa anabolic ndi machitidwe a catabolic.Poganizira mfundo imeneyi, kugwiritsa ntchito mankhwala ena abwino achilengedwe kumatha kukhala kopambana kuti mukhale ndi thanzi labwino.PRP chifukwa imatulutsa mapulateleti α- Zinthu za kukula zomwe zili mu granules zimagwiritsidwa ntchito kwambiri poyang'anira kuthekera kwa kusintha kwa minofu, zomwe zimachepetsanso ululu.Ndipotu, chimodzi mwa zolinga zazikulu za chithandizo cha PRP ndikuyimitsa tizilombo toyambitsa matenda ndi catabolic microenvironment ndikulimbikitsa kusintha kwa mankhwala oletsa kutupa.Olemba ena adawonetsa kale kuti thrombin activated PRP imawonjezera kutulutsidwa kwa mamolekyu angapo achilengedwe.Zinthu izi zikuphatikizapo hepatocyte kukula factor (HGF) ndi tumor necrosis factor (TNF- α), Transforming growth factor beta1 (TGF- β 1), vascular endothelial growth factor (VEGF) ndi epidermis Growth factor (EGF).Kafukufuku wina wasonyeza kuti PRP imalimbikitsa kuwonjezeka kwa mtundu wa ii collagen ndi milingo ya aggrecan mRNA, pamene kuchepetsa kuletsa kwa pro-inflammatory cytokine interleukin - (IL) 1 pa iwo.Zinanenedwanso kuti chifukwa cha HGF ndi TNF- α [28] PRP ingathandize kukhazikitsa anti-inflammatory effect.Zokonzekera zonse ziwirizi zimachepetsa mphamvu ya nyukiliya kappaB (NF- κВ) Anti activation ntchito ndi kufotokozera;Kachiwiri, kudzera mu mawu a TGF- β 1 amalepheretsanso chemotaxis ya monocyte, motero imatsutsana ndi TNF- α Zotsatira za kusintha kwa chemokines.HGF ikuwoneka kuti ili ndi gawo lofunikira kwambiri pakuletsa kutupa komwe kumayambitsidwa ndi PRP.Cytokine yotsutsa-yotupayi imawononga njira yowonetsera NF- κ B ndi proinflammatory cytokine expression imalepheretsa kuyankha kwa kutupa.Kuphatikiza apo, PRP imathanso kuchepetsa kuchuluka kwa nitric oxide (NO).Mwachitsanzo, mu articular cartilage, kuwonjezeka kwa NO ndende kwatsimikiziridwa kuti kuletsa collagen kaphatikizidwe ndi kuyambitsa chondrocyte apoptosis, ndikuwonjezera kaphatikizidwe ka matrix metalloproteinases (MMPs), potero kulimbikitsa kusintha kwa catabolism.Pankhani ya kuwonongeka kwa maselo, PRP imaganiziridwanso kuti imatha kuyendetsa autophagy ya mitundu yeniyeni ya maselo.Akafika ku ukalamba womaliza, magulu ena a maselo amataya kuthekera kwa static state ndikudzikonzanso.Komabe, kafukufuku waposachedwa wasonyeza kuti chithandizo cha PRP chingathe kusintha zinthu zovulazazi.Moussa ndi anzake adatsimikizira kuti PRP ikhoza kulimbikitsa chitetezo cha chondrocytes mwa kuwonjezera zizindikiro za autophagy ndi anti-inflammatory, pamene kuchepetsa apoptosis ya osteoarthritis cartilage ya anthu.Garcia Pratt et al.Zimanenedwa kuti autophagy imatsimikizira kusintha pakati pa kupumula ndi kukalamba tsogolo la minofu tsinde maselo.Ofufuzawo amakhulupirira kuti, mu vivo, kukhazikika kwa autophagy yophatikizika kumapewa kudzikundikira kwa kuwonongeka kwa intracellular ndikuletsa kukalamba ndi kuchepa kwa magwiridwe antchito a maselo a satana.Ngakhale mu ukalamba wa maselo amtundu waumunthu, monga posachedwa, Parrish ndi Rodes aperekanso zopindulitsa kwambiri, kuwonetsanso mphamvu zotsutsana ndi zotupa za PRP.Panthawiyi, cholinga chake ndi kuyanjana pakati pa mapulateleti ndi neutrophils.Pakufufuza kwawo, ofufuzawo adalongosola kuti mapulateleti opangidwa ndi arachidonic acid adatengedwa ndi neutrophils ndikusandulika kukhala leukotrienes ndi prostaglandins, omwe amadziwika kuti ndi mamolekyu otupa.Komabe, kuyanjana kwa platelet neutrophil kumapangitsa kuti leukotriene isanduke ma lipoproteins, omwe atsimikiziridwa kuti ndi othandiza kwambiri oletsa kutupa omwe amatha kuchepetsa kutsegulira kwa neutrophils ndikuletsa dialysis, ndikulimbikitsa cholowa mpaka kumapeto kwa machiritso.

The proinflammatory microenvironment imasokoneza machiritso.Chovuta kwambiri ndichakuti ntchito yayikulu ya proteinase imalepheretsa zochitika zachilengedwe za kukula kwa chinthu (GF).Kuphatikiza pa mitotic, angiogenic ndi chemotactic properties, PRP imakhalanso gwero lazinthu zambiri zakukula.Ma biomolecules awa amatha kuthana ndi zotsatira zoyipa m'matenda otupa poletsa kutupa komanso kukhazikitsa kukondoweza kwa anabolic.

 

Ma cell Factor

Ma Cytokines mu PRP amagwira ntchito yofunika kwambiri pakuwongolera njira yokonzanso minofu ndikuwongolera kuwonongeka kotupa.Ma anti-inflammatory cytokines ndi mamolekyu osiyanasiyana a biochemical omwe amayankhira kuyankha kwa proinflammatory cytokines, makamaka chifukwa cha ma macrophages.Ma anti-inflammatory cytokines amalumikizana ndi ma cytokine inhibitors ndi ma soluble cytokine receptors kuti athetse kutupa.Interleukin (IL) - 1 receptor antagonists, IL-4, IL-10, IL-11 ndi IL-13 amatchulidwa ngati mankhwala oletsa kutupa, ma cytokines.Malingana ndi mitundu yosiyanasiyana ya mabala, ma cytokines ena, monga interferon, leukemia inhibitory factor, TGF- β Ndi IL-6, omwe angasonyeze zotsatira zowononga kapena zowononga.TNF- α, IL-1 ndi IL-18 ali ndi ma cytokine receptors, omwe angalepheretse proinflammatory zotsatira za mapuloteni ena [37].IL-10 ndi imodzi mwama cytokines othandiza kwambiri odana ndi kutupa, omwe amatha kutsitsa ma cytokines a proinflammatory monga IL-1, IL-6 ndi TNF- α, ndikuwongolera zinthu zotsutsana ndi kutupa.Njira zotsutsana ndi zowongolerazi zimagwira ntchito yofunika kwambiri popanga komanso kugwira ntchito kwa ma cytokines oyambitsa matenda.Kuphatikiza apo, ma cytokines ena amatha kuyambitsa mayankho amtundu wina kuti alimbikitse ma fibroblasts, omwe ndi ofunikira pakukonzanso minofu.Kutupa kwa cytokine TGF β 1, IL-1 β, IL-6, IL-13 ndi IL-33 kumalimbikitsa fibroblasts kusiyanitsa myofibroblasts ndikusintha ECM [38].Komanso, ma fibroblasts amatulutsa cytokine TGF- β, IL-1 β, IL-33, CXC ndi CC chemokines zimalimbikitsa kuyankha kwa kutupa mwa kuyambitsa ndi kulemba maselo a chitetezo cha mthupi monga macrophages.Maselo otupawa amagwira ntchito zingapo pabalapo, makamaka polimbikitsa kuchotsedwa kwa bala - ndi biosynthesis ya chemokines, metabolites ndi kukula kwa zinthu, zomwe ndizofunikira kwambiri pakumanganso minyewa yatsopano.Chifukwa chake, ma cytokines mu PRP amagwira ntchito yofunika kwambiri polimbikitsa kuyankha kwa chitetezo chamthupi chamtundu wa cell komanso kulimbikitsa kuchepa kwa gawo lotupa.Ndipotu, ochita kafukufuku ena adasankha njirayi ngati "kutupa koyambitsanso", kusonyeza kuti kutupa, ngakhale kuti wodwalayo ali ndi nkhawa, ndizofunikira komanso zofunikira kwambiri kuti athe kumaliza bwino njira yokonza minofu, poganizira njira ya epigenetic yomwe kutupa kumasonyeza. kulimbikitsa ma cell plasticity.

Udindo wa ma cytokines mu kutupa kwa khungu la fetal ndi wofunikira kwambiri pakufufuza kwamankhwala obwezeretsanso.Kusiyana pakati pa njira zochiritsira za fetal ndi zazikulu ndikuti minyewa yowonongeka ya fetal nthawi zina imabwerera ku chikhalidwe chawo choyambirira malinga ndi msinkhu wa fetal ndi mitundu yoyenera ya minofu.Mwa anthu, khungu la mwana wosabadwayo limatha kuyambiranso mkati mwa milungu 24, pomwe mwa akulu, kuchira kwa zilonda kungayambitse kupanga zipsera.Monga tadziwira, poyerekeza ndi minyewa yathanzi, mawotchi amtunduwu amachepetsedwa kwambiri, ndipo ntchito zawo ndizochepa.Chisamaliro chapadera chimaperekedwa ku cytokine IL-10, yomwe imapezeka kuti imawonetsedwa kwambiri mu amniotic fluid ndi khungu la fetal, ndipo zatsimikiziridwa kuti zimathandizira kukonza khungu la fetal popanda zipsera, zomwe zimalimbikitsidwa ndi pleiotropic effect ya cytokine.ZgheibC et al.Kuyika kwa khungu la fetal kukhala transgenic knockout (KO) IL-10 mbewa ndi mbewa zowongolera zidaphunziridwa.IL-10KO mbewa zinawonetsa zizindikiro za kutupa ndi kupangika kwa zipsera mozungulira ma grafts, pamene ma grafts mu gulu lolamulira sanawonetse kusintha kwakukulu kwa zinthu za biomechanical komanso kuchiritsa zipsera.

Kufunika kowongolera kusamalidwa bwino pakati pa ma cytokines odana ndi kutupa ndi oyambitsa kutupa ndikuti omaliza, akapangidwa mochulukira, pamapeto pake amatumiza zizindikiro za kuwonongeka kwa maselo pochepetsa mawonekedwe a majini ena.Mwachitsanzo, mu mankhwala a musculoskeletal, IL-1 β Down imayendetsa SOX9, yomwe imayambitsa chitukuko cha cartilage.SOX9 imapanga zinthu zofunika zolembera za chitukuko cha cartilage, imayang'anira mtundu wa II collagen alpha 1 (Col2A1), ndipo imayang'anira encoding mtundu wa II collagen majini.IL-1 β Pomaliza, mawu a Col2A1 ndi aggrecan adachepetsedwa.Komabe, chithandizo ndi mankhwala opangidwa ndi mapulateleti asonyezedwa kuti amaletsa IL-1 β Akadali wothandizira wotheka wa mankhwala obwezeretsanso kuti apitirize kufotokoza za majini a collagen coding ndi kuchepetsa apoptosis ya chondrocytes yopangidwa ndi proinflammatory cytokines.

Kukondoweza kwa Anabolic: Kuwonjezera pa kulamulira mkhalidwe wotupa wa minofu yowonongeka, ma cytokines mu PRP nawonso amatenga nawo mbali muzochita za anabolic pochita ntchito zawo za mitosis, kukopa mankhwala ndi kufalikira.Uwu ndi kafukufuku wa in vitro wotsogozedwa ndi Cavallo et al.Kuphunzira zotsatira za PRPs zosiyanasiyana pa chondrocytes anthu.Ofufuzawo adawona kuti zinthu za PRP zokhala ndi mapulateleti otsika kwambiri komanso kuchuluka kwa leukocyte kumalimbikitsa zochitika za chondrocyte, zomwe zimathandizira kulimbikitsa njira zama cell za anabolic.Mwachitsanzo, mawonekedwe a mtundu wa II collagen ndi ma glycans ophatikizana adawonedwa.Mosiyana ndi izi, kuchuluka kwa mapulateleti ndi leukocyte kumawoneka kuti kumalimbikitsa njira zina zama cell zomwe zimakhudzana ndi ma cytokines osiyanasiyana.Olembawo amanena kuti izi zikhoza kukhala chifukwa cha kukhalapo kwa maselo ambiri oyera m'magazi a PRP.Maselowa amawoneka kuti ndi omwe amachititsa kuti zinthu zina zikule, monga VEGF, FGF-b, ndi interleukins IL-1b ndi IL-6, zomwe zingathe kulimbikitsa TIMP-1 ndi IL-10.Mwa kuyankhula kwina, poyerekeza ndi "zoipa" PRP formula, osakaniza PRP wolemera mu mapulateleti ndi maselo oyera a magazi amawoneka kuti amalimbikitsa kusokoneza kwa ma chondrocyte.

Kafukufuku wopangidwa ndi Schnabel et al.idapangidwa kuti iwunikire gawo la autologous biomaterials mu minofu ya tendon ya akavalo.Olembawo adasonkhanitsa zitsanzo za magazi ndi tendon kuchokera ku akavalo akuluakulu asanu ndi limodzi (zaka 2-4), ndipo adayang'ana pa kafukufuku wa gene expression pattern, DNA ndi collagen zomwe zili mu tendon explants za flexor digitorum superficialis za akavalo omwe amakula mkatikati mwa PRP. kapena mankhwala ena a magazi.Kutulutsa kwa tendon kunakula m'magazi, plasma, PRP, platelet deficient plasma (PPP) kapena ma aspirates a m'mafupa (BMA), ndipo ma amino acid anawonjezeredwa ku 100%, 50% kapena 10% seramu yaulere DMEM.Poyendetsa kusanthula kwa biochemical komwe kumagwiritsidwa ntchito pambuyo ..., ofufuzawo adawona kuti TGF- β Kuphatikizika kwa PDGF-BB ndi PDGF-1 mu PRP sing'anga kunali kwakukulu kwambiri kuposa kwazinthu zonse zamagazi zomwe zidayesedwa.Kuonjezera apo, minyewa ya tendon yomwe imabzalidwa mu 100% PRP sing'anga inawonetsa kuwonjezeka kwa jini ya mapuloteni a matrix COL1A1, COL3A1 ndi COMP, koma sanawonjezere ma enzymes a catabolic MMPs3 ndi 13. Osachepera potengera kapangidwe ka tendon, izi mu vivo kuphunzira kumathandizira kugwiritsa ntchito autolo - mankhwala osokoneza bongo, kapena PRP, pofuna kuchiza matenda aakulu a mammalian tendinitis.

Chen et al.Zotsatira zokonzanso za PRP zinakambidwanso.M'maphunziro awo apitalo, ochita kafukufuku adatsimikizira kuti, kuwonjezera pa kupititsa patsogolo mapangidwe a cartilage, PRP inalimbikitsanso kuwonjezeka kwa kaphatikizidwe ka ECM ndikuletsa kutupa kwa articular cartilage ndi nucleus pulposus.PRP ikhoza kuyambitsa TGF kudzera mu phosphorylation ya Smad2 / 3- β Signal njira imakhala ndi gawo lofunikira pakukula kwa maselo ndi kusiyanitsa.Kuonjezera apo, amakhulupiriranso kuti ziphuphu za fibrin zomwe zimapangidwira pambuyo poyambitsa PRP zimapereka mawonekedwe olimba amitundu itatu, zomwe zimathandiza kuti maselo azitsatira, zomwe zingayambitse kumanga minofu yatsopano.

Ofufuza ena athandiza kwambiri pochiza zilonda zapakhungu zosatha pa nkhani ya dermatology.Izi nazonso ndi zochititsa chidwi.Mwachitsanzo, kafukufuku wopangidwa ndi Hessler ndi Shyam mu 2019 akuwonetsa kuti PRP ndiyofunika ngati njira yochiritsira yotheka komanso yothandiza, pomwe zilonda zosamva mankhwala zimadzetsabe mavuto azachuma pazaumoyo.Makamaka, zilonda zam'mimba za matenda a shuga ndi vuto lalikulu lodziwika bwino la thanzi, lomwe limapangitsa kuti miyendo ikhale yosavuta kudulidwa.Kafukufuku wofalitsidwa ndi Ahmed et al.mu 2017 adawonetsa kuti autologous PRP gel imatha kulimbikitsa machiritso kwa odwala omwe ali ndi zilonda zam'mimba zodwala matenda ashuga mwa kutulutsa zinthu zofunika kukula, potero zimathandizira kuchira.Mofananamo, Gonchar ndi anzake adawunikiranso ndikukambirana za kuthekera kwa PRP ndi kukula kwa cocktails pakuwongolera chithandizo cha zilonda zamapazi a shuga.Ofufuzawo adanena kuti kugwiritsa ntchito zosakaniza za kukula kungakhale njira yothetsera vuto, yomwe ingapangitse ubwino wogwiritsa ntchito PRP ndi kukula kwachinthu chimodzi.Choncho, poyerekeza ndi kugwiritsa ntchito chinthu chimodzi cha kukula, kuphatikiza kwa PRP ndi njira zina zothandizira kungathandize kwambiri machiritso a zilonda zam'mimba.

 

Fibrin

Mapulateleti amakhala ndi zinthu zingapo zokhudzana ndi dongosolo la fibrinolytic, lomwe limatha kuwongolera kapena kutsika kuwongolera kachitidwe ka fibrinolytic.Ubale wa nthawi ndi kuthandizira kwapang'onopang'ono kwa zigawo za hematological ndi ntchito ya mapulateleti pakuwonongeka kwa magazi ndi vuto loyenera kukambirana mozama m'deralo.Mabukuwa amayambitsa maphunziro ambiri omwe amangoganizira za mapulateleti, omwe amadziwika kuti amatha kukhudza machiritso.Ngakhale pali maphunziro ambiri apamwamba, zigawo zina za hematological, monga coagulation factor ndi fibrinolytic systems, zapezeka kuti zikuthandizira kwambiri kukonza mabala.Mwa kutanthauzira, fibrinolysis ndi njira yovuta yachilengedwe yomwe imadalira kuyambitsa kwa michere ina kuti ipititse patsogolo kuwonongeka kwa fibrin.Fibrinolysis reaction yaperekedwa ndi olemba ena kuti zinthu zowononga ma fibrin (fdp) zitha kukhala ma cell omwe amathandizira kukonza minofu.Zotsatira za zochitika zofunika zamoyo m'mbuyomu zimachokera ku fibrin ndikuchotsa angiogenesis, zomwe ndizofunikira kuti chilonda chichiritsidwe.Mapangidwe a magazi pambuyo povulazidwa amakhala ngati chitetezo chotetezera minyewa kuti asatayike magazi ndi kuukira kwa tizilombo toyambitsa matenda, komanso amapereka matrix osakhalitsa omwe maselo amatha kusamuka panthawi yokonza.Kutsekeka kwa magazi kumachitika chifukwa cha fibrinogen yomwe imang'ambika ndi serine protease, ndipo mapulateleti amasonkhanitsidwa mu mesh yolumikizana ndi fibrin fiber.Izi zinayambitsa kupangidwa kwa polymerization ya fibrin monomer, yomwe ndizochitika zazikulu za kupanga magazi.Chophimbacho chimatha kugwiritsidwanso ntchito ngati nkhokwe ya ma cytokines ndi zinthu zomwe zimakulirakulira, zomwe zimatulutsidwa pakuwonongeka kwa mapulateleti oyendetsedwa.Dongosolo la fibrinolytic limayendetsedwa mosamalitsa ndi plasmin, ndipo limagwira ntchito yofunika kwambiri polimbikitsa kusamuka kwa maselo, bioavailability ya zinthu zakukula komanso kuwongolera machitidwe ena a protease omwe amakhudzidwa ndi kutupa kwa minofu ndi kusinthika.Zigawo zazikulu za fibrinolysis, monga urokinase plasminogen activator receptor (uPAR) ndi plasminogen activator inhibitor-1 (PAI-1), zimadziwika kuti zimawonetsedwa m'maselo a mesenchymal stem cell (MSCs), omwe ndi maselo apadera ofunikira kuti chilonda chichiritsidwe bwino. .

 

Kusamuka kwa Maselo

Kutsegula kwa plasminogen kudzera mu mgwirizano wa uPA uPAR ndi njira yomwe imathandizira kusamuka kwa maselo otupa chifukwa imapangitsa kuti proteolysis ipangidwe.Chifukwa cha kusowa kwa ma transmembrane ndi ma intracellular domains, uPAR imafunikira ma co receptor monga integrin ndi vitellin kuti azitha kuwongolera kusamuka kwa ma cell.Inanenanso kuti kumangidwa kwa uPA uPAR kudapangitsa kuti pakhale mgwirizano wa uPAR wa vitrectonectin ndi integrin, zomwe zimalimbikitsa kumamatira kwa ma cell.Plasminogen activator inhibitor-1 (PAI-1) nayonso imapangitsa kuti ma cell adzitseke.Ikamangiriza ku uPA ya uPA upar integrin complex pa cell surface, imawononga kuyanjana pakati pa upar vitellin ndi integrin vitellin.

Pankhani ya mankhwala obwezeretsanso, maselo amtundu wa mesenchymal tsinde amasonkhanitsidwa kuchokera ku fupa la fupa pakawonongeka kwakukulu kwa chiwalo, kotero kuti angapezeke pakuyenda kwa odwala omwe ali ndi fractures angapo.Komabe, nthawi zina, monga kulephera kwa aimpso kumapeto, kulephera kwa chiwindi, kapena kukanidwa pambuyo pa kuikidwa kwa mtima, maselowa sangawoneke m'magazi [66].Chochititsa chidwi n'chakuti mafupa aumunthuwa adachokera ku maselo a mesenchymal (stromal) omwe sakanatha kudziwika m'magazi a anthu athanzi [67].Udindo wa uPAR polimbikitsa ma cell a mesenchymal stem cell (BMSCs) adanenedwa kale, zomwe ndi zofanana ndi zomwe zimachitika uPAR polimbikitsa ma cell a hematopoietic stem cell (HSCs).Varabaneni et al.Zotsatira zake zidawonetsa kuti kugwiritsa ntchito granulocyte colony-stimulating factor mu mbewa zoperewera za uPAR zidalephereka MSC, zomwe zidalimbitsanso gawo lothandizira la fibrinolysis system pakusuntha kwama cell.Kafukufuku wina adawonetsanso kuti glycosyl phosphatidylinositol anchored uPA receptors imayang'anira kumamatira, kusamuka, kuchulukana ndi kusiyanitsa mwa kuyambitsa njira zina zolumikizirana ndi ma cell, motere: phosphatidylinositol 4,5-diphosphate 3-kinase/Akt2 ndi ERK1. (FAK).

Pankhani yakuchiritsa mabala a MSC, fibrinolytic factor yatsimikizira kufunikira kwake.Mwachitsanzo, mbewa zoperewera za plasminogen zinawonetsa kuchedwa kwakukulu kwa zochitika za machiritso a bala, kusonyeza kuti plasmin inali yofunika kwambiri.Mwa anthu, kutayika kwa plasmin kungayambitsenso zovuta za kuchira kwa bala.Kusokonezeka kwa magazi kumatha kulepheretsa kwambiri kusinthika kwa minofu, zomwe zikufotokozeranso chifukwa chake njira zosinthikazi zimakhala zovuta kwambiri kwa odwala matenda a shuga.

Maselo a mafupa a mesenchymal stem anatengedwa kupita kumalo a bala kuti apititse patsogolo kuchira.Pamalo okhazikika, ma cellwa adawonetsa uPAuPAR ndi PAI-1.Mapuloteni awiri otsiriza ndi hypoxia inducible factor α (HIF-1 α) Kutsata ndikosavuta chifukwa HIF-1 mu MSCs α Kutsegula kwa FGF-2 ndi HGF kumalimbikitsa kulamulira kwa FGF-2 ndi HGF;HIF-2 α Nayenso, VEGF-A [77] imayendetsedwa bwino, yomwe pamodzi imathandizira kuchiritsa mabala,.Kuphatikiza apo, HGF ikuwoneka kuti ikuthandizira kulembera maselo amtundu wa mesenchymal m'mafupa m'malo ovulala molumikizana.Tiyenera kuzindikira kuti ischemic ndi hypoxic mikhalidwe yasonyezedwa kuti imasokoneza kwambiri kukonza mabala.Ngakhale ma BMSC amakonda kukhala m'minofu yomwe imapereka mpweya wochepa, kupulumuka kwa ma BMSC osiyidwa mu vivo kumakhala kochepa chifukwa ma cell omwe amawaika nthawi zambiri amafa pamikhalidwe yoyipa yomwe imawonedwa mu minofu yowonongeka.Tsogolo la kumamatira ndi kupulumuka kwa maselo a m'mafupa a mesenchymal tsinde pansi pa hypoxia zimadalira zinthu za fibrinolytic zomwe zimatulutsidwa ndi maselowa.PAI-1 ili ndi kuyanjana kwakukulu kwa vitellin, kotero imatha kupikisana kuti imangirire uPAR ndi integrin ku vitellin, potero imalepheretsa kusamuka kwa ma cell ndi kusamuka.

PRF

Monocyte ndi Regeneration System

Malinga ndi mabuku, pali zokambirana zambiri za udindo wa monocytes mu machiritso a bala.Macrophages makamaka amachokera ku magazi a monocyte ndipo amagwira ntchito yofunika kwambiri pamankhwala obwezeretsanso [81].Chifukwa neutrophils secrete IL-4, IL-1, IL-6 ndi TNF- α, Maselo amenewa nthawi zambiri kudutsa bala za 24-48 maola kuvulala.Mapulateleti amatulutsa thrombin ndi platelet factor 4 (PF4), yomwe imatha kulimbikitsa kulembedwa kwa ma monocyte ndikusiyanitsa ma macrophages ndi ma cell a dendritic.Chinthu chofunika kwambiri cha macrophages ndi pulasitiki yawo, ndiko kuti, amatha kusintha ma phenotypes ndi kusiyanitsa mu mitundu ina ya maselo, monga maselo a endothelial, ndiyeno amasonyeza ntchito zosiyanasiyana kuzinthu zosiyana siyana za biochemical mu chilonda cha microenvironment.Maselo otupa amasonyeza ma phenotypes awiri akuluakulu, M1 kapena M2, malingana ndi chizindikiro cha maselo am'deralo monga gwero la chilimbikitso.Ma macrophages a M1 amapangidwa ndi tizilombo toyambitsa matenda, kotero amakhala ndi zotsatira zowononga kwambiri.Mosiyana ndi izi, ma macrophages a M2 nthawi zambiri amapangidwa ndi machitidwe amtundu wa 2 ndipo amakhala ndi anti-inflammatory properties, omwe amadziwika ndi kuwonjezeka kwa IL-4, IL-5, IL-9, ndi IL-13.Zimakhudzidwanso ndi kukonza minofu mwa kupanga zinthu za kukula.Kusintha kuchokera ku M1 kupita ku M2 subtype kumayendetsedwa makamaka ndi gawo lomaliza la machiritso a bala.M1 macrophages amayambitsa neutrophil apoptosis ndikuyambitsa kuchotsedwa kwa maselowa).The phagocytosis ya neutrophils imayendetsa zochitika zingapo, momwe kupanga ma cytokines kumazimitsidwa, polarizing macrophages ndikutulutsa TGF-β 1. Kukula kumeneku ndikowongolera kofunikira pakusiyanitsa kwa myofibroblast ndi kutsika kwa bala, komwe kumathandizira kuthetsa kutupa ndi kutupa. kuyambika kwa gawo lochulukirachulukira pakuchiritsa machiritso [57].Puloteni ina yokhudzana kwambiri ndi ma cell ndi serine (SG).Ma cell a hemopoietic secretory granule proteoglycan apezeka kuti ndi ofunikira kuti asunge mapuloteni obisika m'maselo apadera a chitetezo chamthupi, monga ma mast cell, neutrophils ndi cytotoxic T lymphocytes.Ngakhale kuti maselo ambiri omwe sali a hematopoietic amakhalanso ndi plasminogen, maselo onse otupa amatulutsa mapuloteni ambiri ndikuwasungira mu granules kuti apitirize kuyanjana ndi oyimira pakati otupa, kuphatikizapo ma proteases, cytokines, chemokines ndi kukula.Unyolo wa glycosaminoglycan (GAG) woyipa kwambiri ku SG akuwoneka kuti ndi wofunikira kwambiri pakukhazikika kwa ma granules obisika, chifukwa amatha kumangirira ndikuthandizira kusungidwa kwa zigawo za granular zomwe zimayikidwa mu cell, protein, ndi GAG mwanjira yeniyeni.Ponena za kutenga nawo mbali pa kafukufuku wa PRP, Woulfe ndi anzake adawonetsa kale kuti kusowa kwa SG kumagwirizana kwambiri ndi kusintha kwa mapulateleti a morphological;Platelet factor 4 β- Zowonongeka za kusunga PDGF mu thromboglobulin ndi mapulateleti;Kusanjika bwino kwa mapulateleti ndi katulutsidwe mu vitro ndi vuto la thrombosis mu vivo.Chifukwa chake ofufuzawo adatsimikiza kuti proteoglycan iyi ikuwoneka kuti ndiyomwe imayambitsa thrombosis.

Fibrinolytic

Mankhwala olemera a Platelet amatha kutenga magazi athunthu kudzera mu kusonkhanitsa ndi centrifugation, ndikugawa osakanizawo m'magulu osiyanasiyana okhala ndi plasma, mapulateleti, maselo oyera amagazi ndi maselo oyera amagazi.Pamene ndende ya mapulateleti ndi apamwamba kuposa mtengo wapatali, imatha kufulumizitsa kukula kwa mafupa ndi minofu yofewa, ndi zotsatira zochepa.Kugwiritsa ntchito mankhwala a autologous PRP ndi sayansi yatsopano yazachilengedwe, yomwe yawonetsa mosalekeza zotsatira zabwino polimbikitsa ndi kuchiritsa kuvulala kwamitundu yosiyanasiyana.Kuchita bwino kwa njira ina yochiritsirayi kungabwere chifukwa cha kuperekedwa kwapafupi kwa zinthu zosiyanasiyana za kukula ndi mapuloteni kuti ayese ndikuthandizira kuchiritsa mabala a thupi ndi kukonza minofu.Kuphatikiza apo, dongosolo la fibrinolytic mwachiwonekere limakhudza kwambiri kukonza minofu yonse.Kuphatikiza pa kusintha kwa maselo opangira maselo otupa ndi ma cell a mafupa a mesenchymal tsinde, imathanso kuwongolera ntchito ya proteolytic ya malo ochiritsa bala komanso kusinthika kwa minofu ya mesodermal, kuphatikiza mafupa, cartilage ndi minofu, chifukwa chake ndi gawo lofunikira kwambiri mankhwala a minofu ndi mafupa.

Kuchiritsa kofulumira ndi cholinga chomwe akatswiri ambiri azachipatala amatsatira.PRP imayimira chida chabwino chachilengedwe, chomwe chikupitiriza kupereka chitukuko cholimbikitsa pakulimbikitsa ndi kugwirizanitsa zochitika zowonongeka.Komabe, chifukwa chida ichi chochiritsira chikadali chovuta kwambiri, makamaka chifukwa chimatulutsa zinthu zosawerengeka za bioactive ndi njira zawo zosiyanasiyana zogwirira ntchito ndi zotsatira zowonetsera zizindikiro, kufufuza kwina kumafunika.

(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: Dec-16-2022