Namhlanje, ingcamango eyaziwa ngokuba yi-PRP yaqala ukubonakala kwinkalo ye-hematology ngo-1970.I-Hematologists yenze igama elithi PRP kumashumi eminyaka edlulileyo ukuchaza i-plasma efunyenwe kwi-platelet count ephezulu kunexabiso elisisiseko legazi le-peripheral.Ngaphezulu kweminyaka elishumi kamva, i-PRP yayisetyenziselwa utyando lwe-maxillofacial njengendlela yeplatelet rich fibrin (PRF).Umxholo we-fibrin kule mveliso ye-PRP inexabiso elibalulekileyo ngenxa yokubambelela kwayo kunye neempawu ezizinzileyo, ngelixa i-PRP iye yagcina iipropati ezichasayo kwaye ivuselela ukwanda kweeseli.Ekugqibeleni, malunga ne-1990s, i-PRP yaqala ukuduma.Ekugqibeleni, obu bugcisa butshintshelwe kwezinye iinkalo zonyango.Ukusukela ngoko, olu hlobo lwebhayoloji elungileyo luye lwafundwa ngokubanzi kwaye lusetyenziswa kunyango lwezonzakala ezahlukeneyo ze-musculoskeletal zabadlali abaqeqeshiweyo, nto leyo eyakhuthaza ngakumbi ukuqwalaselwa kwayo ngokubanzi kumajelo eendaba.Ngaphandle kokuphumelela kwi-orthopedics kunye neyeza lezemidlalo, i-PRP iphinda isetyenziswe kwi-ophthalmology, i-gynecology, i-urology kunye ne-cardiology, i-pediatrics kunye nokuhlinzwa kweplastiki.Kwiminyaka yakutshanje, i-PRP iye yadunyiswa ngabadermatologists ngokukwazi kwayo ukunyanga izilonda zesikhumba, ukulungiswa kwesikhumba, ukuvuselelwa kwezicubu, ukuvuselelwa kwesikhumba kunye nokulahlekelwa kweenwele.
Ukuqwalasela into yokuba i-PRP inokulawula ngokuthe ngqo iinkqubo zokuphulukisa kunye nokuvuvukala, kuyimfuneko ukuzisa i-cascade yokuphulukisa njengesalathiso.Inkqubo yokuphulukisa ihlukaniswe ngamanqanaba amane alandelayo: i-hemostasis;Ukukrala;Ukwandiswa kweeseli kunye ne-matrix, kwaye ekugqibeleni ukulungiswa kwenxeba.
Ukunyangwa kwezicubu
I-tissue yokuphulukisa i-cascade reaction iyasebenza, ekhokelela ekuhlanganiseni kweplatelet Ukubunjwa kwamahlwili kunye nokuphuhliswa kwe-matrix ye-extracellular yesikhashana (ECM).Emva koko, iiplatelet zibambelela kwi-collagen eveziweyo kunye neprotheni ye-ECM, ebangela ukukhululwa kwee-molecule ze-bioactive ezikhoyo kwi-granules.Iiplatelets ziqulethe iindidi ze-bioactive molecules, kubandakanywa izinto zokukhula, izinto ze-chemotherapy kunye ne-cytokines, kunye nabalamli be-proinflammatory, njenge-prostaglandin, i-prostate cyclin, i-histamine, i-thromboxane, i-serotonin kunye ne-bradykinin.
Inqanaba lokugqibela lenkqubo yokuchacha lixhomekeke ekulungisweni kwenxeba.Ukulungiswa kwezicubu kulawulwa ngokungqongqo ukuseka ibhalansi phakathi kwe-anabolic kunye ne-catabolic reactions.Kule nqanaba, i-platelet-derived growth factor (PDGF) kunye nokuguqula ukukhula (TGF- β) i-Fibronectin kunye ne-fibronectin ivuselela ukwanda kunye nokufuduka kwe-fibroblasts, kunye nokuhlanganiswa kwamacandelo e-ECM.Nangona kunjalo, ixesha lokuvuthwa kwenxeba lixhomekeke kumlinganiselo omkhulu kubunzima benxeba, iimpawu zomntu ngamnye kunye nokukwazi ukuphiliswa kwezicubu ezonzakeleyo.Ezinye izinto ze-pathophysiological kunye ne-metabolic inokuchaphazela inkqubo yokuphilisa, njenge-tissue ischemia, i-hypoxia, usulelo, ukungalingani kwemeko yokukhula, kunye nezifo ezinxulumene ne-metabolic syndrome.
I-proinflammatory microenvironment iphazamisa inkqubo yokuphulukisa.Okuntsonkothileyo kukuba umsebenzi ophezulu weprotease unqanda isenzo sendalo sokukhula kwemeko (GF).Ukongeza kwiipropathi zayo ze-mitotic, i-angiogenic kunye ne-chemotactic, i-PRP ikwangumthombo ocebileyo wezinto ezininzi zokukhula.Ezi biomolecules zinokuchasana nemiphumo eyingozi kwizicubu ezivuthayo ngokulawula ukwanda kokuvuvukala kunye nokuseka i-anabolic stimuli.Ukuthathela ingqalelo ezi mpawu, abaphandi banokufumana amandla amakhulu ekunyangeni ukonzakala okwahlukeneyo.
Izifo ezininzi, ngakumbi ezo zendalo ye-musculoskeletal, zixhomekeke kakhulu kwiimveliso zezinto eziphilayo ezilawula inkqubo yokuvuvukala, njenge-PRP yonyango lwe-osteoarthritis.Kule meko, impilo ye-articular cartilage ixhomekeke kwibhalansi echanekileyo ye-anabolic kunye ne-catabolic reactions.Ngalo mgaqo engqondweni, ukusetyenziswa kweearhente ezithile zebhayoloji ezinobungqina bempumelelo ekuphumezeni ulungelelwaniso olusempilweni.I-PRP kuba ikhupha iiplatelet α- Izinto zokukhula eziqulethwe kwiigranules zisetyenziselwa ngokubanzi ukulawula amandla okuguqulwa kwezicubu, ezinciphisa intlungu.Enyanisweni, enye yeenjongo eziphambili zonyango lwe-PRP kukuyeka i-microenvironment evuthayo kunye ne-catabolic kunye nokukhuthaza ukuguqulwa kweziyobisi ezichasayo.Abanye ababhali baye babonisa ngaphambili ukuba i-thrombin isebenze i-PRP yonyusa ukukhululwa kweeamolekyu ezininzi zezinto eziphilayo.Ezi zinto ziquka i-hepatocyte factor factor (HGF) kunye ne-tumor necrosis factor (TNF- α) , Ukuguqula ukukhula kwe-beta1 (TGF- β 1), i-vascular endothelial growth factor (VEGF) kunye ne-epidermis Growth factor (EGF).Olunye uphando luye lwabonisa ukuba i-PRP ikhuthaza ukwanda kohlobo lwee-collagen kunye ne-aggrecan mRNA amanqanaba, ngelixa linciphisa ukuvinjelwa kwe-pro-inflammatory cytokine interleukin - (IL) 1 kubo.Kwaye kwacetyiswa ukuba ngenxa ye-HGF kunye ne-TNF- α [28] i-PRP inokunceda ukuseka i-anti-inflammatory effect.Omabini la malungiselelo eemolekyuli anciphisa i-nuclear factor kappaB (NF- κВ) Anti activation umsebenzi kunye nokubonakalisa;Okwesibini, ngokusebenzisa i-TGF- β 1 inkcazo iphinda ithintele i-monocyte chemotaxis, ngaloo ndlela iphikisana ne-TNF- α Effect kwi-transactivation ye-chemokines.I-HGF ibonakala idlala indima ebaluleke kakhulu kwimpembelelo echasayo eyenziwa yi-PRP.Le cytokine enamandla echasayo iyonakalisa i-NF- κ B indlela yokubonakalisa iimpawu kunye ne-proinflammatory cytokine expression inhibit impendulo yokuvuvukala.Ukongezelela, i-PRP inokunciphisa izinga eliphezulu le-nitric oxide (NO).Ngokomzekelo, kwi-articular cartilage, ukunyuka kwe-NO concentration kubonakaliswe ukuthintela i-collagen synthesis kunye ne-chondrocyte apoptosis, ngelixa inyusa ukuhlanganiswa kwe-matrix metalloproteinases (MMPs), ngaloo ndlela ikhuthaza ukuguqulwa kwe-catabolism.Ngokubhekiselele kwi-cell degeneration, i-PRP iphinda iqwalaselwe ukuba ikwazi ukulawula i-autophagy yeentlobo ezithile zeeseli.Xa ufikelela kwimo yokugqibela yokuguga, amanye amaqela eeseli aphulukana nokubakho kwimeko engatshintshiyo kunye nokuzihlaziya.Nangona kunjalo, uphononongo lwakutsha nje lubonise ukuba unyango lwe-PRP lunokuziguqula ezi meko ziyingozi.UMoussa kunye noogxa babonisa ukuba i-PRP inokubangela ukukhuselwa kwe-chondrocytes ngokunyusa i-autophagy kunye ne-anti-inflammatory markers, ngelixa inciphisa i-apoptosis ye-osteoarthritis cartilage yabantu.UGarcia Pratt et al.Kuxelwe ukuba i-autophagy imisela utshintsho phakathi kokuphumla kunye nokuguga kwe-muscle stem cells.Abaphandi bakholelwa ukuba, kwi-vivo, i-normalization ye-autophagy edibeneyo igwema ukuqokelela umonakalo we-intracellular kunye nokuthintela ukuguga kunye nokuncipha kokusebenza kweeseli zesathelayithi.Nangona iiseli ze-stem zabantu eziguga, njengakutsha nje, i-Parrish kunye ne-Rodes nazo zenze igalelo elibalulekileyo, ngokuqhubekayo ukutyhila amandla okulwa nokuvuvukala kwe-PRP.Ngeli xesha, kugxilwe kwintsebenziswano phakathi kweeplatelet kunye neutrophils.Kuphando lwabo, abaphandi bachaza ukuba iiplatelets ezisebenzayo ezikhutshwe yi-arachidonic acid zixutywe yi-neutrophils kwaye ziguqulwa zibe yi-leukotrienes kunye ne-prostaglandins, eyaziwa ngokuba yi-molecule evuthayo.Nangona kunjalo, i-platelet neutrophil interaction ivumela i-leukotriene ukuba iguqulwe ibe yi-lipoproteins, ebonakaliswe ukuba yiprotheni esebenzayo echasayo enokunciphisa ukusebenza kwe-neutrophils kunye nokukhusela i-dialysis, kwaye ikhuthaze ilifa ukuya kwinqanaba lokugqibela le-cascade yokuphulukisa.
I-proinflammatory microenvironment iphazamisa inkqubo yokuphulukisa.Okuntsonkothileyo kukuba umsebenzi ophezulu weprotease unqanda isenzo sendalo sokukhula kwemeko (GF).Ukongeza kwiipropathi zayo ze-mitotic, i-angiogenic kunye ne-chemotactic, i-PRP ikwangumthombo ocebileyo wezinto ezininzi zokukhula.Ezi biomolecules zinokuchasana nemiphumo eyingozi kwizicubu ezivuthayo ngokulawula ukwanda kokuvuvukala kunye nokuseka i-anabolic stimulation.
Umba weSeli
I-Cytokines kwi-PRP idlala indima ephambili ekulawuleni inkqubo yokulungiswa kwezicubu kunye nokulawula umonakalo ovuthayo.I-cytokines ezichasayo ziluhlu olubanzi lweeamolekyu ze-biochemical ezidibanisa impendulo ye-cytokines e-proinflammatory, ebangelwa ngokukodwa yi-macrophages esebenzayo.Ii-cytokines ezichasayo zisebenzisana ne-cytokine inhibitors ezithile kunye ne-soluble cytokine receptors ukulawula ukuvuvukala.I-Interleukin (IL) - i-1 ye-receptor antagonists, i-IL-4, i-IL-10, i-IL-11 kunye ne-IL-13 ihlelwa njengezona zidakamizwa ezichasayo, i-cytokines.Ngokweentlobo zamanxeba ahlukeneyo, ezinye ii-cytokines, ezifana ne-interferon, i-leukemia inhibitory factor, i-TGF- β kunye ne-IL-6, engabonisa imiphumo ye-proinflammatory okanye anti-inflammatory.I-TNF- α, IL-1 kunye ne-IL-18 ine-receptors ethile ye-cytokine, enokuthintela umphumo we-proinflammatory wezinye iiprotheni [37].I-IL-10 yenye yezona cytokines ezichasayo ezichasayo, ezinokuhla zilawula i-cytokines e-proinflammatory ezifana ne-IL-1, i-IL-6 kunye ne-TNF- α， Kwaye phezulu ulawule izinto ezichasayo.Ezi ndlela zokulwa nokulawula zidlala indima ephambili kwimveliso kunye nomsebenzi we-cytokines ene-proinflammatory.Ukongeza, ii-cytokines ezithile zinokubangela iimpendulo zemiqondiso ethile ukuvuselela ii-fibroblasts, ezibaluleke kakhulu ekulungisweni kwezicubu.I-cytokine evuthayo ye-TGF β 1, IL-1 β, IL-6, IL-13 kunye ne-IL-33 ivuselela i-fibroblasts ukuba ihluke kwi-myofibroblasts kunye nokuphucula i-ECM [38].Ngaloo ndlela, i-fibroblasts ikhupha i-cytokine TGF- β, IL-1 β, IL-33, iCXC kunye neCC chemokines ikhuthaza ukusabela okuvuthayo ngokusebenza kunye nokugaya iiseli ze-immune ezifana ne-macrophages.Ezi seli ezivuthayo zidlala iindima ezininzi kwinxeba, ngokukodwa ngokukhuthaza ukukhutshwa kwenxeba - kunye ne-biosynthesis ye-chemokines, i-metabolites kunye nezinto ezikhulayo, ezibalulekileyo ekwakhiweni ngokutsha kwezicubu ezintsha.Ngoko ke, i-cytokines kwi-PRP idlala indima ebalulekileyo ekukhuthazeni uhlobo lwe-cell mediated impendulo ye-immune kunye nokukhuthaza ukubuyiswa kwesigaba sokuvuvukala.Enyanisweni, abanye abaphandi batyumba le nkqubo ngokuthi "ukuvutha okuvuselelekayo", ebonisa ukuba inqanaba lokuvuvukala, nangona isigulane sixhalabile, linyathelo eliyimfuneko kunye nelibalulekileyo lokugqiba ngempumelelo inkqubo yokulungiswa kwezicubu, kuthathelwa ingqalelo indlela ye-epigenetic ebonisa ukuvutha. ukukhuthaza iplastiki yeeseli.
Indima ye-cytokines ekudumbeni kwesikhumba somntwana ibaluleke kakhulu kuphando lweyeza lokuvuselela.Umahluko phakathi kweendlela zokuphulukisa umntwana kunye nabantu abadala kukuba izicubu zomntwana ezonakalisiweyo ngamanye amaxesha zibuyela kwimeko yazo yangaphambili ngokweminyaka yomntwana kunye neentlobo zezicubu ezifanelekileyo.Kubantu, ulusu lomntwana luyakwazi ukuvuselela ngokupheleleyo kwiiveki ezingama-24, ngelixa kubantu abadala, ukuphulukiswa kwenxeba kunokukhokelela ekwakhekeni kwesikhumba.Njengoko siyazi, xa kuthelekiswa nezicubu eziphilileyo, iipropathi zomatshini zezicubu ezinobunzima ziyancipha kakhulu, kwaye imisebenzi yazo ilinganiselwe.Ingqwalasela ekhethekileyo ihlawulwa kwi-cytokine IL-10, efunyenwe ukuba ibonakaliswe kakhulu kwi-amniotic fluid kunye nesikhumba somntwana, kwaye ibonakaliswe ukuba idlala indima ekulungisweni kwamahhala kwesikhumba somntwana, ekhuthazwa yimpembelelo ye-pleiotropic ye-cytokine.ZgheibC et al.Ukutshintshwa kwesikhumba somntwana kwi-transgenic knockout (KO) IL-10 iigundane kunye neegundane zokulawula zafundwa.I-IL-10KO iigundane zibonise iimpawu zokuvuvukala kunye nokwakheka kwezibazi malunga ne-grafts, ngelixa i-grafts kwiqela lolawulo libonisa ukuba akukho lutshintsho olubalulekileyo kwiipropati ze-biomechanical kwaye akukho ukuphulukiswa kwesilonda.
Ukubaluleka kokulawula ibhalansi ethambileyo phakathi kokubonakaliswa kwe-cytokines echasayo kunye ne-pro-inflammatory kukuba le yokugqibela, xa iveliswe ngokugqithisileyo, ekugqibeleni ithumela imiqondiso yokuthotywa kweeseli ngokunciphisa ukubonakaliswa kofuzo oluthile.Ngokomzekelo, kwiyeza ze-musculoskeletal, i-IL-1 β Down ilawula i-SOX9, ejongene nokuphuhliswa kwe-cartilage.I-SOX9 ivelisa izinto ezibalulekileyo zokubhaliweyo zokuphuhliswa kwe-cartilage, ilawula uhlobo lwe-II i-collagen alpha 1 (Col2A1), kwaye inoxanduva lwe-encoding type II collagen genes.I-IL-1 β Ekugqibeleni, ukubonakaliswa kwe-Col2A1 kunye ne-aggrecan kwancipha.Nangona kunjalo, unyango oluneemveliso ezityebileyo zeplatelet lubonakaliswe ukuba luthintele i-IL-1 β Kusengumlingani onokwenzeka weyeza lokuvuselela ukugcina ukubonakaliswa kwe-collagen coding genes kunye nokunciphisa i-apoptosis ye-chondrocytes eyenziwa yi-cytokines ye-proinflammatory.
Ukuvuselela i-Anabolic: Ngaphandle kokulawula imeko yokuvuvukala kwezicubu ezonakalisiweyo, i-cytokines kwi-PRP nayo ithatha inxaxheba kwi-anabolic reaction ngokudlala indima yabo ye-mitosis, ukukhanga kweekhemikhali kunye nokwanda.Olu luphononongo lwe-in vitro olukhokelwa nguCavallo et al.Ukufunda imiphumo yee-PRP ezahlukeneyo kwi-chondrocytes yabantu.Abaphandi baqaphela ukuba iimveliso ze-PRP ezineplatelet ephantsi kunye ne-leukocyte concentrations ivuselela umsebenzi oqhelekileyo we-chondrocyte, ofanelekileyo ekukhuthazeni ezinye iindlela zeselula zokuphendula kwe-anabolic.Umzekelo, ukubonakaliswa kohlobo ii-collagen kunye ne-aggregating glycans yabonwa.Ngokwahlukileyo, ugxininiso oluphezulu lweeplatelet kunye ne-leukocyte zibonakala zivuselela ezinye iindlela zokubonisa iiseli ezibandakanya ii-cytokines ezahlukeneyo.Ababhali bacetyisa ukuba oku kungenxa yobukho benani elikhulu leeseli ezimhlophe zegazi kule fom ye-PRP ethile.Ezi seli zibonakala zinoxanduva lokubonisa ukwanda kwezinto ezithile zokukhula, ezifana neVEGF, FGF-b, kunye ne-interleukins IL-1b kunye ne-IL-6, enokuthi ivuselele i-TIMP-1 kunye ne-IL-10.Ngamanye amazwi, xa kuthelekiswa nefomula ye-PRP "embi", umxube we-PRP otyebileyo kwiiplatelet kunye neeseli ezimhlophe zegazi zibonakala zikhuthaza ukuhlaselwa kwe-chondrocytes.
Uphononongo oluyilwe nguSchnabel et al.yenzelwe ukuvavanya indima ye-autologous biomaterials kwi-tendon yehashe.Ababhali baqokelela iisampulu zegazi kunye ne-tendon kumahashe amathandathu amadala (iminyaka eyi-2-4 ubudala), kwaye bagxile kufundo lwepateni yokuchazwa kofuzo, i-DNA kunye nomxholo we-collagen we-tendon explants ye-flexor digitorum superficialis yamahashe akhuliswe phakathi aqukethe i-PRP. okanye ezinye iimveliso zegazi.I-tendon explants yakhuliswa kwigazi, i-plasma, i-PRP, i-platelet deficient plasma (PPP) okanye i-bone marrow aspirates (BMA), kunye ne-amino acids yongezwa kwi-100%, i-50% okanye i-10% ye-serum yamahhala ye-DMEM.Ekuqhubeni uhlalutyo olusebenzayo lwe-biochemical emva ..., abaphandi baqaphele ukuba i-TGF- β Ukuxinwa kwe-PDGF-BB kunye ne-PDGF-1 kwi-PRP medium yayiphezulu kakhulu kunezo zonke ezinye iimveliso zegazi ezivavanyiweyo.Ukongezelela, izicubu ze-tendon ezikhuliswe kwi-100% ye-PRP ephakathi zibonise ukwanda kwe-gene expression of matrix proteins COL1A1, COL3A1 kunye ne-COMP, kodwa ayizange ikhulise i-enzyme ye-catabolic MMPs3 kunye ne-13. Ubuncinane ngokubhekiselele kwisakhiwo se-tendon, oku kwi-vivo isifundo sixhasa ukusetyenziswa i-autolo - imveliso yegazi ye-gouty, okanye i-PRP, yonyango lwe-tendinitis enkulu ye-mammalian.
UChen et al.Isiphumo sokuvuselela i-PRP saxoxwa ngakumbi.Kuluhlu lwabo lwangaphambili lwezifundo, abaphandi babonisa ukuba, ngaphezu kokuphucula ukubunjwa kwe-cartilage, i-PRP nayo yakhuthaza ukwanda kwe-ECM synthesis kwaye inqanda ukusabela okuvuthayo kwe-articular cartilage kunye ne-nucleus pulposus.I-PRP inokwenza i-TGF isebenze nge-phosphorylation ye-Smad2 / 3- β Indlela yomqondiso idlala indima ebalulekileyo ekukhuleni kweeseli kunye nokuhlukana.Ukongezelela, kukholelwa ukuba i-fibrin clots eyenziwe emva kokusebenza kwe-PRP ibonelela ngesakhiwo esiqinileyo sesithathu-dimensional, esenza ukuba iiseli zibambelele, ezinokukhokelela ekwakhiweni kwezicubu ezintsha.
Abanye abaphandi baye benza igalelo elikhulu kunyango lwezilonda ezingapheliyo zesikhumba kwi-dermatology.Oku nako kuyaphawuleka.Umzekelo, uphando olwenziwa nguHessler kunye noShyam ngo-2019 lubonisa ukuba i-PRP inexabiso njengonyango olunokwenzeka nolusebenzayo, ngelixa isilonda esinganyangekiyo ngamachiza sisazisa umthwalo omkhulu wezoqoqosho kukhathalelo lwempilo.Ngokukodwa, i-diabetes foot ulcer yingxaki enkulu eyaziwayo yezempilo, eyenza amalungu alula ukuba anqunyulwe.Uphononongo olupapashwe ngu-Ahmed et al.kwi-2017 ibonise ukuba i-autologous PRP gel inokukhuthaza ukuphulukiswa kwesilonda kwizigulane ezinezilonda ezingapheliyo zesifo sikashukela ngokukhupha izinto eziyimfuneko zokukhula, ngaloo ndlela ziphucula kakhulu izinga lokuphulukisa.Ngokufanayo, uGonchar kunye noogxa bahlaziywa kwaye baxubusha amandla okuvuselela i-PRP kunye ne-cocktail factor cocktails ekuphuculeni unyango lwezilonda zeenyawo zesifo sikashukela.Abaphandi bacebise ukuba ukusetyenziswa kwezinto ezixutywayo zokukhula kunokwenzeka ukuba kube isisombululo esinokwenzeka, esinokuphucula izibonelelo zokusebenzisa i-PRP kunye nokukhula okukodwa.Ngoko ke, xa kuthelekiswa nokusetyenziswa kwento enye yokukhula, ukudibanisa kwe-PRP kunye nezinye izicwangciso zonyango kunokukhuthaza kakhulu ukuphulukiswa kwezilonda ezingapheliyo.
Fibrin
Iiplatelets zithwala izinto ezininzi ezinxulumene nenkqubo ye-fibrinolytic, enokuthi inyuke ilawule okanye ihle ilawule ukusabela kwe-fibrinolytic.Ubudlelwane bexesha kunye negalelo elihambelanayo lamacandelo e-hematological kunye nomsebenzi weplatelet kwi-clot degradation kuseyingxaki efanele ukuxoxwa ngokubanzi kuluntu.Uncwadi luzisa izifundo ezininzi ezijolise kuphela kwiiplatelet, ezidume ngokukwazi ukuchaphazela inkqubo yokuphilisa.Ngaphandle kwenani elikhulu lezifundo ezibalaseleyo, ezinye iinxalenye ze-hematological, ezifana ne-coagulation factor kunye ne-fibrinolytic systems, nazo zifunyenwe zinegalelo elikhulu ekulungiseni amanxeba asebenzayo.Ngokwenkcazo, i-fibrinolysis yinkqubo yezinto eziphilayo eziyinkimbinkimbi exhomekeke ekusebenziseni i-enzymes ethile ukukhuthaza ukuthotywa kwe-fibrin.Ukusabela kwe-Fibrinolysis kuye kwacetywa ngabanye ababhali ukuba iimveliso zokuthotywa kwe-fibrin (fdp) ngokwenene zinokuba zii-agent ze-molecular ezijongene nokuvuselela ukulungiswa kwezicubu.Ukulandelelana kweziganeko ezibalulekileyo zebhayoloji ngaphambili zivela kwi-fibrin deposition kunye nokususwa kwe-angiogenesis, eyimfuneko yokuphilisa inxeba.Ukubunjwa kwamahlwili emva kokulimala kusebenza njengoluhlu olukhuselayo lokukhusela izicubu ekulahlekeni kwegazi kunye nokuhlasela kwe-microbial agents, kwaye inika kwakhona i-matrix yesikhashana apho iiseli zinokufuduka ngexesha lokulungiswa.Ihlwili kungenxa yefibrinogen ecandwe yi-serine protease, kwaye iiplatelet ziqokelelwa kumnatha wefibrin odityaniswe ngokunqamlezileyo.Oku kusabela kubangele i-polymerization ye-fibrin monomer, esona siganeko siphambili sokwakheka kwehlwili legazi.I-clot ingasetyenziselwa njenge-reservoir ye-cytokines kunye nezinto ezikhulayo, ezikhutshwa ngexesha lokuchithwa kweeplatelet ezisebenzayo.Inkqubo ye-fibrinolytic ilawulwa ngokungqongqo yi-plasmin, kwaye idlala indima ephambili ekukhuthazeni ukufuduka kweeseli, i-bioavailability yezinto ezikhulayo kunye nokulawulwa kwezinye iinkqubo zeprotease ezibandakanyekayo ekudumbeni kwezicubu kunye nokuvuselelwa.Izinto eziphambili ze-fibrinolysis, ezifana ne-urokinase plasminogen activator receptor (uPAR) kunye ne-plasminogen activator inhibitor-1 (PAI-1), ziyaziwa ukuba zibonakaliswe kwiiseli ze-mesenchymal stem (MSCs), ezizintlobo zeeseli ezikhethekileyo eziyimfuneko ekuphulukisweni kwesilonda. .
Ukufuduka kweeSeli
Ukusebenza kwe-plasminogen ngokusebenzisa i-UPA uPAR association yinkqubo ekhuthaza ukufuduka kweeseli ezivuthayo kuba iphakamisa i-proteolysis ye-extracellular.Ngenxa yokungabikho kwe-transmembrane kunye ne-intracellular domains, i-uPAR idinga i-co receptors ezifana ne-integrin kunye ne-vitellin ukulawula ukufuduka kweeseli.Iphinde yabonisa ukuba ukudityaniswa kwe-UPA uPAR kubangele ukwanda kwi-affinity ye-UPAR ye-vitrectonectin kunye ne-integrin, ekhuthaza ukunamathela kweeseli.I-Plasminogen activator inhibitor-1 (PAI-1) yenza ukuba iiseli zihlukane.Xa ibophelela kwi-UPA ye-upar integrin complex kumphezulu weseli, itshabalalisa intsebenziswano phakathi kwe-upar vitellin kunye ne-integrin vitellin.
Kwimeko yeyeza lokuvuselela, i-bone marrow mesenchymal stem cells ihlanganiswa ukusuka kumathambo kwimeko yomonakalo omkhulu womzimba, ngoko ke inokufumaneka kwi-circulation yezigulane ezinezahlulo ezininzi.Nangona kunjalo, kwiimeko ezithile, ezifana nokungaphumeleli kwesigxina sokugqibela, ukungaphumeleli kwesibindi sokugqibela, okanye ngexesha lokulahlwa emva kokutshintshwa kwentliziyo, ezi seli azinakubonwa egazini [66].Okubangel 'umdla kukuba, la mathambo omntu athathwe kwi-mesenchymal (stromal) ye-progenitor cell ayikwazanga ukufunyanwa kwigazi labantu abasempilweni [67].Indima ye-UPAR ekuhlanganiseni i-bone marrow mesenchymal stem cells (BMSCs) iphakanyisiwe ngaphambili, efana nesiganeko se-uPAR ekuhlanganiseni iiseli ze-hematopoietic stem cells (HSCs).Varabaneni et al.Iziphumo zibonise ukuba ukusetyenziswa kwe-granulocyte colony-stimulating factor in uPAR defective mice kubangele ukusilela kwe-MSC, okwaphinda komeleza indima exhasayo yenkqubo ye-fibrinolysis ekufudukeni kweeseli.Uphononongo olongezelelweyo lubonise ukuba i-glycosyl phosphatidylinositol i-anchored uPA receptors ilawula ukunamathela, ukufuduka, ukwanda kunye nokwahlula ngokusebenzisa iindlela ezithile zokubonisa i-intracellular, ngolu hlobo lulandelayo: i-phosphatidylinositol ephilayo i-4,5-diphosphate 3-kinase / i-Akt kunye ne-adhesion kinase1, (FAK).
Kumxholo wokuphiliswa kwesilonda se-MSC, i-fibrinolytic factor ibonakalise ukubaluleka kwayo ngakumbi.Ngokomzekelo, iigundane ezinqongopheleyo ze-plasminogen zibonise ukulibaziseka okukhulu kwiziganeko zokuphulukisa amanxeba, ezibonisa ukuba i-plasmin ibalulekile kule nkqubo.Ebantwini, ukulahlekelwa yiplasmin nako kunokukhokelela kwiingxaki zokuphiliswa kwenxeba.Ukuphazamiseka kokuhamba kwegazi kunokuthintela kakhulu ukuvuselelwa kwezicubu, ezikwachaza ukuba kutheni ezi nkqubo zokuhlaziywa zinzima kakhulu kwizigulane ezinesifo sikashukela.
Iiseli ze-Bone marrow mesenchymal stem zagaywa kwindawo yenxeba ukukhawulezisa ukuphiliswa kwenxeba.Phantsi kweemeko ezizinzileyo, ezi seli zivakalise uPAuPAR kunye ne-PAI-1.Iiprotheni ezimbini zokugqibela ziyi-hypoxia inducible factor α (HIF-1 α) Ukujolisa kulula kakhulu kuba i-HIF-1 kwi-MSCs α Ukusetyenziswa kwe-FGF-2 kunye ne-HGF kukhuthaze ukulawulwa kwe-FGF-2 kunye ne-HGF;I-HIF-2 α Emva koko, i-VEGF-A [77] i-up-regulated, edibeneyo inegalelo ekuphulukiseni amanxeba,.Ukongeza, i-HGF ibonakala iphucula ukufunwa kweeseli zethambo zomongo we-mesenchymal kwiindawo zamanxeba ngendlela ye-synergistic.Kufuneka kuqatshelwe ukuba iimeko ze-ischemic kunye ne-hypoxic zibonakaliswe ukuba ziphazamise kakhulu ukulungiswa kwesilonda.Nangona ii-BMSCs zidla ngokuhlala kwizicubu ezibonelela ngamanqanaba asezantsi eoksijini, ukusinda kwee-BMSCs ezitshintshwayo kwi-vivo kuncipha kuba iiseli ezitshintshiweyo zihlala zifa phantsi kweemeko ezimbi ezibonwa kwizicubu ezonakeleyo.Ikamva lokubambelela kunye nokusinda kweeseli ze-mesenchymal stem zomongo phantsi kwe-hypoxia kuxhomekeke kwizinto ze-fibrinolytic ezifihliweyo zezi seli.I-PAI-1 inobudlelwane obuphezulu be-vitellin, ngoko inokukhuphisana ngokubophelela kwe-uPAR kunye ne-integrin kwi-vitellin, ngaloo ndlela inqanda ukunamathela kweseli kunye nokufuduka.
I-Monocyte kunye neNkqubo yokuHlaziya
Ngokutsho kweencwadi, kukho iingxoxo ezininzi malunga nendima ye-monocytes ekuphulukiseni isilonda.I-Macrophages ikakhulu ivela kwi-monocytes yegazi kwaye idlala indima ebalulekileyo kunyango lokuvuselela [81].Ngenxa yokuba i-neutrophils ikhupha i-IL-4, i-IL-1, i-IL-6 kunye ne-TNF- α, Ezi seli zihlala zingena enxebeni malunga neeyure ezingama-24-48 emva kokulimala.Iiplatelets zikhupha i-thrombin kunye ne-platelet factor 4 (PF4), enokukhuthaza ukuqeshwa kwe-monocytes kwaye ihluke kwii-macrophages kunye neeseli ze-dendritic.Isici esibalulekileyo se-macrophages yiplastiki yabo, oko kukuthi, banokuguqula i-phenotypes kwaye bahluke kwezinye iintlobo zeeseli, ezifana neeseli ze-endothelial, kwaye emva koko zibonise imisebenzi eyahlukeneyo kwi-biochemical stimuli kwi-microenvironment yesilonda.Iiseli ezivuthayo zivakalisa i-phenotypes ezimbini ezinkulu, i-M1 okanye i-M2, kuxhomekeke kwisignali ye-molecular yendawo njengomthombo wokuvuselela.I-M1 macrophages ibangelwa yi-microbial agents, ngoko ke banemiphumo engakumbi ye-proinflammatory.Ngokwahlukileyo, i-M2 macrophages idla ngokuveliswa ngohlobo lwe-2 reactions kwaye ineempawu ezichasayo, ezibonakaliswa ngokunyuka kwe-IL-4, IL-5, IL-9, kunye ne-IL-13.Ikwabandakanyeka ekulungiseni izicubu ngokuveliswa kwezinto zokukhula.Ukutshintsha ukusuka kwi-M1 ukuya kwi-M2 subtype iqhutywe kakhulu kwinqanaba lokugqibela lokuphulukiswa kwesilonda.I-M1 macrophages ibangela i-neutrophil apoptosis kwaye iqalise ukucocwa kwezi seli).I-phagocytosis ye-neutrophils ivuselela uchungechunge lweziganeko, apho ukuveliswa kwe-cytokines icinyiwe, i-polarizing macrophages kunye nokukhulula i-TGF-β 1. Lo mbandela wokukhula ungumlawuli oyintloko wokuhlukana kwe-myofibroblast kunye nokunciphisa isilonda, esivumela isisombululo sokuvuvukala kunye nokuvuvukala. ukuqaliswa kwesigaba sokwanda kwi-cascade yokuphilisa [57].Enye iprotheni enxulumene kakhulu ebandakanyeka kwiinkqubo zeselula yi-serine (SG).Le hemopoietic cell secretory granule proteoglycan ifunyenwe iyimfuneko yokugcina iiprotheyini ezifihlakeleyo kwiiseli ezithile zokuzivikela, ezifana neeseli ze-mast, i-neutrophils kunye ne-cytotoxic T lymphocytes.Nangona iiseli ezininzi ezingezizo i-hematopoietic nazo zenza i-plasminogen, zonke iiseli ezivuthayo zivelisa isixa esikhulu sale proteni kwaye zigcinwe kwiigranules ukuze ziqhubeke nokusebenzisana nabanye abalamli abavuthayo, kubandakanya i-proteases, i-cytokines, i-chemokines kunye nezinto zokukhula.Amatyathanga e-glycosaminoglycan (GAG) ahlawuliswa kakubi kwi-SG abonakala ebaluleke kakhulu kuzinzo lwe-granules eyimfihlo, njengoko inokubophelela kwaye iququzelele ukugcinwa kwamacandelo e-granular ahlawuliswa ngokuyimfuneko kwiseli, iprotheni, kunye ne-GAG chain chain.Ngokumalunga nokuthatha kwabo inxaxheba kuphando lwe-PRP, uWoulfe kunye noogxa baye babonisa ngaphambili ukuba ukusilela kwe-SG kuhambelana ngokusondeleyo notshintsho lwe-platelet morphological;I-Platelet factor 4 β- Iziphene zokugcinwa kwePDGF kwi-thromboglobulin kunye neeplatelet;Ukuhlanganiswa kweplatelet engalunganga kunye ne-secretion in vitro kunye ne-thrombosis defect kwi-vivo.Ngoko ke abaphandi bagqiba ukuba le proteoglycan ibonakala iyona nto ilawula i-thrombosis.
Iimveliso ezityebileyo zePlatelet zinokufumana igazi lobuqu ngokuqokelelwa kunye ne-centrifugation, kwaye zahlule umxube kwiimaleko ezahlukeneyo eziqulethe iplasma, iiplatelets, iiseli ezimhlophe zegazi kunye neeseli ezimhlophe zegazi.Xa i-concentration yeplatelet iphezulu kunexabiso elisisiseko, inokukhawulezisa ukukhula kwamathambo kunye nezicubu ezithambileyo, kunye nemiphumo emincinci.Ukusetyenziswa kweemveliso ze-PRP ezizenzekelayo yi-biotechnology entsha, ebonise ngokuqhubekayo iziphumo ezithembayo ekukhuthazeni nasekuphuculeni ukuphiliswa kokulimala kwezicubu ezahlukeneyo.Ukusebenza kwale ndlela yonyango yolunye unyango kunokubangelwa ukuhanjiswa kwendawo yoluhlu olubanzi lwezinto ezikhulayo kunye neeprotheni ukulinganisa kunye nokuxhasa ukuphulukiswa kwesilonda somzimba kunye nenkqubo yokulungiswa kwezicubu.Ukongeza, inkqubo ye-fibrinolytic ngokucacileyo inefuthe elibalulekileyo kuwo wonke ukulungiswa kwezicubu.Ukongeza ekutshintsheni ukuqeshwa kweeseli ezivuthayo kunye neeseli ze-mesenchymal stem zomongo wamathambo, inokulawula umsebenzi weproteolytic weendawo zokuphulukisa amanxeba kunye nenkqubo yokuhlaziywa kwezicubu ze-mesodermal, kubandakanya ithambo, i-cartilage kunye nezihlunu, ngoko ke yinxalenye ephambili iyeza le-musculoskeletal.
Ukuphiliswa okukhawulezileyo yinjongo elandelwa kakhulu ziingcali ezininzi kwicandelo lezonyango.I-PRP imele isixhobo esihle se-biological, esiqhubeka nokubonelela ngophuhliso oluthembisayo ekukhuthazeni nasekulungelelaniseni i-cascade yeziganeko zokuvuselela.Nangona kunjalo, ngenxa yokuba esi sixhobo sonyango sisenzima kakhulu, ngakumbi kuba sikhupha izinto ezingenakubalwa ze-bioactive kunye neendlela ezahlukeneyo zokusebenzisana kunye nemiphumo yokudluliselwa komqondiso, uphando olongezelelweyo luyafuneka.
(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: Dec-16-2022