Kumvetsetsa Kwatsopano kwa Platelet Rich Plasma Therapy (PRP) - Gawo II

PRP Yamakono: "Clinical PRP"

M'zaka 10 zapitazi, ndondomeko ya chithandizo ya PRP yasintha kwambiri.Kudzera mu kafukufuku woyesera komanso wazachipatala, tsopano tikumvetsetsa bwino za mapulateleti ndi ma cell physiology.Kuonjezera apo, kafukufuku wambiri wamakono, kuwunika kwa meta ndi mayesero oyendetsedwa mwachisawawa asonyeza mphamvu ya PRP biotechnology m'madera ambiri azachipatala, kuphatikizapo dermatology, opaleshoni ya mtima, opaleshoni ya pulasitiki, opaleshoni ya mafupa, kusamalira ululu, matenda a msana, ndi mankhwala a masewera. .

Makhalidwe apano a PRP ndi kuchuluka kwake kwa mapulateleti, komwe kumasintha kuchokera ku tanthauzo loyambirira la PRP (kuphatikiza kuchuluka kwa mapulateleti apamwamba kuposa mtengo woyambira) kupita ku 1 × 10 6/µ L kapena pafupifupi ka 5 kuchuluka kwa mapulateleti ocheperako m'mapulateleti kuchokera. zoyambira.Mukuwunikanso kwakukulu kwa Fadadu et al.Machitidwe a 33 PRP ndi ma protocol adawunikidwa.Chiwerengero cha mapulateleti cha kukonzekera komaliza kwa PRP kopangidwa ndi ena mwa machitidwewa ndi otsika kuposa a magazi onse.Iwo adanena kuti chiwerengero cha platelet cha PRP chinawonjezeka chochepa kwambiri monga 0.52 ndi single spin kit (Selphyl ®).Mosiyana ndi zimenezi, kusinthasintha kawiri EmCyte Genesis PurePRPII ® Kuphatikizika kwa mapulateleti opangidwa ndi chipangizocho ndipamwamba kwambiri (1.6 × 10 6 /µL) .

Mwachiwonekere, njira za in vitro ndi zinyama simalo abwino ofufuzira kuti asinthe bwino kukhala machitidwe azachipatala.Mofananamo, kafukufuku woyerekeza chipangizocho sichigwirizana ndi chigamulocho, chifukwa amasonyeza kuti chiwerengero cha platelet pakati pa zipangizo za PRP ndizosiyana kwambiri.Mwamwayi, kudzera muukadaulo wopangidwa ndi ma proteomics ndi kusanthula, titha kuwonjezera kumvetsetsa kwathu kwa ntchito zama cell mu PRP zomwe zimakhudza zotsatira za chithandizo.Musanagwirizane pakukonzekera ndi kukhazikitsidwa kwa PRP, PRP iyenera kutsata njira zachipatala za PRP kuti zilimbikitse njira zowonongeka za minofu ndi zotsatira zachipatala zopita patsogolo.

Clinical PRP formula

Pakalipano, PRP (C-PRP) yothandiza kwambiri yachipatala yakhala ikudziwika ngati zovuta zowonongeka zamagulu amtundu wa autologous mu plasma yaing'ono yomwe imachokera ku gawo la magazi ozungulira pambuyo pa centrifugation.Pambuyo pa centrifugation, PRP ndi zigawo zake zopanda mapulateleti zimatha kubwezeredwa kuchokera ku chipangizo cha ndende molingana ndi kachulukidwe ka maselo osiyanasiyana (omwe kachulukidwe ka mapulateleti ndi otsika kwambiri).

Gwiritsani ntchito PurePRP-SP ® Cell density separation equipment (EmCyte Corporation, Fort Myers, FL, USA) idagwiritsidwa ntchito kwa magazi athunthu pambuyo pa njira ziwiri za centrifugation.Pambuyo pa ndondomeko yoyamba ya centrifugation, chigawo chonse cha magazi chinagawidwa m'magulu awiri, kuyimitsidwa kwa plasma (yowonda) ndi maselo ofiira a magazi.Mu A, gawo lachiwiri la centrifugation latha.Voliyumu yeniyeni ya PRP ikhoza kuchotsedwa kuti igwiritsidwe ntchito kwa odwala.Kukula mu B kumasonyeza kuti pali bungwe Mipikisano chigawo erythrocyte sedimentation bulauni wosanjikiza (woyimiridwa ndi buluu mzere) pansi pa zipangizo, amene ali mkulu woipa wa kupatsidwa zinthu za m`mwazi, monocytes ndi lymphocytes, zochokera osalimba gradient.Mu chitsanzo ichi, malinga ndi ndondomeko yokonzekera C-PRP yokhala ndi neutrophils osauka, chiwerengero chochepa cha neutrophils (<0.3%) ndi erythrocytes (<0.1%) chidzachotsedwa.

Platelet granule

Kumayambiriro kwa PRP yachipatala, α- Granules ndizomwe zimatchulidwa kwambiri m'kati mwa mapulateleti, chifukwa zimakhala ndi coagulation factor, chiwerengero chachikulu cha PDGF ndi angiogenic regulators, koma alibe ntchito ya thrombogenic.Zinthu zina ndi monga chemokine ndi cytokine zomwe sizidziwika bwino, monga platelet factor 4 (PF4), pre-platelet basic protein, P-selectin (an activator of integrin) ndi chemokine RANTES (yoyendetsedwa ndi activation, kuwonetsa ma T cell abwinobwino komanso mwina kubisa).Ntchito yonse ya zigawo za granule za mapulateletizi ndikulemba ndi kuyambitsa ma cell ena oteteza thupi kapena kuyambitsa kutupa kwa endothelial cell.

Zigawo zowirira kwambiri za granular monga ADP, serotonin, polyphosphate, histamine ndi adrenaline zimagwiritsidwa ntchito momveka bwino ngati zowongolera mapulateleti ndi thrombosis.Chofunika kwambiri, zambiri mwazinthuzi zimakhala ndi ntchito yosintha maselo a chitetezo chamthupi.Platelet ADP imadziwika ndi P2Y12ADP cholandilira pama cell a dendritic (DC), motero kumawonjezera antigen endocytosis.DC (maselo owonetsera antigen) ndi ofunikira kwambiri poyambitsa kuyankha kwa chitetezo cha T cell ndikuwongolera chitetezo chamthupi choteteza, chomwe chimagwirizanitsa chitetezo cham'mimba ndi chitetezo cha mthupi.Kuonjezera apo, mapulateleti adenosine triphosphate (ATP) amatumiza zizindikiro kudzera mu T cell receptor P2X7, zomwe zimapangitsa kuti ma cell a CD4 T athandizidwe ndi proinflammatory T helper 17 (Th17).Zigawo zina zamtengo wapatali za granule (monga glutamate ndi serotonin) zimapangitsa kuti T cell isamuke ndikuwonjezera kusiyanitsa kwa monocyte kupita ku DC, motsatana.Mu PRP, ma immunomodulators awa opangidwa kuchokera ku tinthu tating'onoting'ono amakhala olemera kwambiri ndipo amakhala ndi chitetezo chambiri.

Chiwerengero cha kuyanjana kwachindunji ndi kosalunjika komwe kungatheke pakati pa mapulateleti ndi ma cell ena (receptor) ndikokwanira.Chifukwa chake, kugwiritsa ntchito PRP m'malo am'deralo kungayambitse zotupa zosiyanasiyana.

Kukhazikika kwa mapulateleti

C-PRP iyenera kukhala ndi milingo yazachipatala ya mapulateleti okhazikika kuti apange machiritso opindulitsa.Mapulateleti mu C-PRP ayenera kulimbikitsa kukula kwa maselo, kaphatikizidwe ka mesenchymal ndi neurotrophic factor, kulimbikitsa kusamuka kwa maselo a chemotactic ndikulimbikitsa ntchito yoteteza chitetezo cha mthupi, monga momwe tawonetsera pa chithunzichi.

Mapulateleti oyendetsedwa, kutulutsidwa kwa PGF ndi mamolekyu omatira kumayimira kuyanjana kosiyanasiyana kwa ma cell: chemotaxis, kumatira kwa ma cell, kusamuka, ndi kusiyanitsa kwa ma cell, ndikuwongolera ntchito zowongolera chitetezo chathupi.Kuyanjana kwa ma cell apulateleti kumathandizira ku angiogenesis ndi ntchito yotupa, ndipo pamapeto pake kumalimbikitsa kukonza minofu.Chidule cha BMA: fupa la mafupa aspirate, EPC: endothelial progenitor cells, EC: endothelial cell, 5-HT: 5-hydroxytryptamine, RANTES: kukhazikitsidwa kwa malamulo a T cell kufotokozera ndi kutsekemera kwapadera, JAM: mtundu wa molekyulu yolumikizira, CD40L: gulu 40 ligand, SDF-1 α: Stromal cell-derived factor-1 α, CXCL: chemokine (CXC motif) ligand, PF4: platelet factor 4. Kuchokera ku Everts et al.

Marx anali munthu woyamba kutsimikizira kuti machiritso a mafupa ndi zofewa analimbikitsidwa, ndipo chiwerengero chochepa cha platelet chinali 1 × 10 6 /µL. 1.3 × Pa 106 mapulateleti/µ L, kafukufukuyu adawonetsa kusakanikirana kochulukirapo.Kuphatikiza apo, Giusti et al.Kuwululidwa 1.5 × Njira yokonza minofu pa mlingo wa 109 imafuna mapulateleti / mL kuti apangitse angiogenesis yogwira ntchito kudzera mu endothelial cell ntchito.Mu kafukufuku womaliza, kuchulukirachulukira kunachepetsa kuthekera kwa angiogenesis kwa mapulateleti mkati ndi mozungulira ma follicles.Kuonjezera apo, deta yoyambirira inasonyeza kuti mlingo wa PRP ungakhudzenso zotsatira za mankhwala.Choncho, pofuna kulimbikitsa kwambiri angiogenesis reaction ndi kulimbikitsa kuchuluka kwa maselo ndi kusamuka kwa maselo, C-PRP iyenera kukhala ndi osachepera 7.5 mu botolo la mankhwala la 5-mL PRP × 10 9 ikhoza kupereka mapulateleti.

Kuphatikiza pa kudalira kwa mlingo, zotsatira za PRP pa ntchito ya selo zikuwoneka kuti zimadalira kwambiri nthawi.Sophie et al.Zotsatirazi zikuwonetsa kuti kuwonetsa kwakanthawi kochepa kwa ma lysates amtundu wa anthu kumatha kuyambitsa kuchuluka kwa maselo a mafupa ndi chemotaxis.M'malo mwake, kuwonetseredwa kwa nthawi yaitali kwa PRP kudzatsogolera kutsika kwa alkaline phosphatase ndi kupanga mchere.

Maselo ofiira a magazi

Maselo ofiira a m’magazi ndi amene ali ndi udindo wotumiza mpweya ku minyewa komanso kusamutsa mpweya woipa kuchokera m’minyewa kupita m’mapapo.Alibe nyukiliyasi ndipo amapangidwa ndi mamolekyu a heme omwe amamangiriza ku mapuloteni.Zigawo za iron ndi heme m’maselo ofiira a m’magazi zimalimbikitsa kuphatikizika kwa mpweya ndi carbon dioxide.Nthawi zambiri, moyo wa maselo ofiira amagazi umakhala pafupifupi masiku 120.Amachotsedwa pakuyenda ndi macrophages kudzera munjira yotchedwa RBC kukalamba.Maselo ofiira a magazi mu zitsanzo za PRP akhoza kuonongeka pansi pa mikhalidwe yometa ubweya (mwachitsanzo, opaleshoni ya magazi athunthu, njira yotetezera chitetezo cha mthupi, kupsinjika kwa okosijeni kapena dongosolo losakwanira la PRP).Chifukwa chake, RBC cell membrane imawola ndikutulutsa hemoglobin (Hb) yapoizoni, yoyesedwa ndi plasma free hemoglobin (PFH), heme ndi iron.].PFH ndi zinthu zake zowonongeka (heme ndi chitsulo) zimatsogolera ku zotsatira zovulaza komanso za cytotoxic pa minofu, zomwe zimayambitsa kupsinjika kwa okosijeni, kutaya kwa nitric oxide, kuyambitsa njira zotupa komanso immunosuppression.Zotsatira izi potsirizira pake zidzatsogolera ku vuto la microcirculation, vasoconstriction m'deralo ndi kuvulala kwa mitsempha, komanso kuwonongeka kwakukulu kwa minofu.

Chofunika kwambiri ndi chakuti pamene RBC yomwe ili ndi C-PRP imaperekedwa ku minofu, imayambitsa zochitika zapanyumba zomwe zimatchedwa eryptosis, zomwe zingayambitse kutulutsidwa kwa cytokine ndi macrophage migration inhibitor.Cytokine iyi imalepheretsa kusamuka kwa monocytes ndi macrophages.Imakhala ndi ma sign amphamvu oletsa kutupa ku minofu yozungulira, imalepheretsa kusamuka kwa ma cell cell ndi kuchuluka kwa fibroblast, ndipo imayambitsa kusagwira bwino ntchito kwa maselo amderalo.Choncho, ndikofunikira kuchepetsa kuipitsidwa kwa RBC mukukonzekera PRP.Kuonjezera apo, ntchito ya maselo ofiira a magazi mu kusinthika kwa minofu siinayambe yadziwika.Kukwanira kwa C-PRP centrifugation ndi kukonzekera ndondomeko kawirikawiri kuchepetsa kapena kuthetsa kukhalapo kwa maselo ofiira a magazi, motero kupewa zotsatira zoipa za hemolysis ndi polycythemia.

Leukocyte mu C-PRP

Kukhalapo kwa maselo oyera a magazi pokonzekera PRP kumadalira zipangizo zothandizira komanso ndondomeko yokonzekera.Mu zipangizo za PRP za plasma, maselo oyera a magazi amachotsedwa kwathunthu;Komabe, maselo oyera a magazi anali okhazikika kwambiri pakukonzekera PRP ya erythrocyte sedimentation brown layer.Chifukwa cha chitetezo cha mthupi komanso chitetezo cha mthupi, maselo oyera amwazi amakhudza kwambiri biology yamkati mwazovuta komanso zosatha.Izi zidzakambidwanso pansipa.Choncho, kukhalapo kwa leukocyte yeniyeni mu C-PRP kungayambitse zotsatira zazikulu za ma cell ndi minofu.Makamaka, machitidwe osiyanasiyana a PRP erythrocyte sedimentation brown-yellow layer layers amagwiritsa ntchito njira zosiyanasiyana zokonzekera, motero amapanga ma neutrophils, lymphocytes ndi monocytes mu PRP.Ma Eosinophils ndi ma basophils sangathe kuyeza pokonzekera PRP chifukwa maselo awo ndi osalimba kwambiri kuti athe kupirira mphamvu zopangira ma centrifugal.

Neutrophils

Neutrophils ndi leukocyte yofunika m'njira zambiri zamachiritso.Njirazi zimaphatikizana ndi mapuloteni oletsa tizilombo toyambitsa matenda omwe amapezeka m'mapulateleti kuti apange chotchinga cholimba motsutsana ndi tizilombo toyambitsa matenda.Kukhalapo kwa neutrophils kumatsimikiziridwa molingana ndi cholinga cha chithandizo cha C-PRP.Kuwonjezeka kwa kutupa kwa minofu kungafunike mu chisamaliro chosachiritsika cha PRP biotherapy kapena ntchito zomwe zimayang'ana kukula kwa mafupa kapena machiritso.Chofunika kwambiri, ntchito zowonjezera za neutrophil zapezeka mu zitsanzo zingapo, kutsindika udindo wawo mu angiogenesis ndi kukonza minofu.Komabe, ma neutrophils amathanso kuyambitsa zovulaza, chifukwa chake sizoyenera kugwiritsa ntchito zina.Zhou ndi Wang adatsimikizira kuti kugwiritsa ntchito PRP yolemera mu neutrophils kungapangitse kuwonjezeka kwa chiŵerengero cha mtundu wa III wa collagen ku mtundu wa I collagen, motero kukulitsa fibrosis ndi kuchepetsa mphamvu ya tendon.Makhalidwe ena owopsa omwe amalumikizidwa ndi neutrophils ndi kutulutsa kwa ma cytokines otupa ndi matrix metalloproteinases (MMPs), omwe amatha kulimbikitsa kutupa ndi catabolism akagwiritsidwa ntchito ku minofu.

Leukomonocyte

Mu C-PRP, ma lymphocyte a T ndi B a mononuclear akhazikika kwambiri kuposa maselo ena oyera a magazi.Iwo ali ogwirizana kwambiri ndi cell-mediated cytotoxic adaptive chitetezo.Ma lymphocyte amatha kuyambitsa kusintha kwa maselo kuti alimbane ndi matenda ndikusintha kuti agwirizane ndi omwe adawaukira.Kuphatikiza apo, T-lymphocyte yochokera ku cytokines (interferon- γ [IFN- γ] Ndipo interleukin-4 (IL-4) imathandizira polarization ya macrophages. Verassar et al. mbewa poyang'anira kusiyanitsa kwa monocytes ndi macrophages.

Monocyte - ma cell amphamvu okonzanso

Malinga ndi chipangizo chokonzekera cha PRP chomwe chimagwiritsidwa ntchito, ma monocyte amatha kutuluka kapena kusakhalapo mu botolo la mankhwala a PRP.Tsoka ilo, machitidwe awo ndi kuthekera kwawo kubadwanso sikukambidwa kawirikawiri m'mabuku.Choncho, chidwi chochepa chimaperekedwa kwa monocytes mu njira yokonzekera kapena njira yomaliza.Gulu la monocyte ndi losiyana, lochokera ku maselo obadwa m'mafupa, ndipo amatumizidwa kuzinthu zotumphukira kudzera mu hematopoietic stem cell pathway malinga ndi microenvironment stimulation.Panthawi ya homeostasis ndi kutupa, ma monocyte ozungulira amachoka m'magazi ndipo amatumizidwa ku minofu yovulala kapena yowonongeka.Atha kukhala ngati macrophages (M Φ) Effector cell kapena cell progenitor cell.Ma Monocyte, macrophages ndi ma dendritic cell amayimira mononuclear phagocytic system (MPS) .M'matenda osokonekera, ma macrophages okhala, zomwe zikukula kwanuko, ma cytokines otupa, ma cell apoptotic kapena necrotic ndi zinthu zazing'onoting'ono zimayambitsa ma monocyte kuti azisiyanitsa m'magulu a cell a MPS.Tiyerekeze kuti pamene C-PRP yomwe ili ndi monocyte yochuluka kwambiri imalowetsedwa mu microenvironment ya matendawa, ma monocyte amatha kusiyanitsa M Φ Kuti apangitse kusintha kwakukulu kwa maselo.

Kuchokera ku monocyte kupita ku M Φ Mu kusintha, yeniyeni M Φ Phenotype.M'zaka khumi zapitazi, chitsanzo chapangidwa, chomwe chimagwirizanitsa M Φ Njira yovuta yotsegulira ikufotokozedwa ngati polarization ya mayiko awiri osiyana: M Φ Phenotype 1 (M Φ 1, Classic activation) ndi M Φ Phenotype 2 (M Φ 2, kuyambitsa kwina).M Φ 1 imadziwika ndi kutupa kwa cytokine secretion (IFN- γ) Ndi nitric oxide kuti apange njira yopha tizilombo toyambitsa matenda.M Φ The phenotype imapanganso vascular endothelial growth factor (VEGF) ndi fibroblast growth factor (FGF).M Φ The phenotype imapangidwa ndi maselo oletsa kutupa omwe ali ndi phagocytosis yapamwamba.M Φ 2 Kupanga zigawo za extracellular matrix, angiogenesis ndi chemokines, ndi interleukin 10 (IL-10).Kuphatikiza pa chitetezo cha tizilombo toyambitsa matenda, M Φ Ikhozanso kuchepetsa kutupa ndikulimbikitsa kukonza minofu.Ndizofunikira kudziwa kuti M Φ 2 yagawidwa kukhala M in vitro Φ 2a, M Φ 2b ndi M Φ 2. Zimatengera kusonkhezera.Mu vivo kumasulira kwa subtypes ndi kovuta chifukwa minofu ikhoza kukhala ndi M Φ Magulu osakanikirana.Chochititsa chidwi n'chakuti, pogwiritsa ntchito zizindikiro za chilengedwe ndi ma IL-4, proinflammatory M Φ 1 ikhoza kutembenuzidwa kuti ilimbikitse kukonza M Φ 2. Kuchokera pazidziwitso izi, ndizomveka kuganiza kuti pali ma monocytes ambiri ndi M Φ C-PRP kukonzekera. angathandize kukonza bwino minofu chifukwa ali ndi anti-yotupa kukonzanso minofu komanso kutulutsa ma cell cell.

Tanthauzo losokoneza la kagawo kakang'ono ka maselo oyera a magazi mu PRP

Kukhalapo kwa maselo oyera a magazi m'mabotolo a mankhwala a PRP kumadalira chipangizo chokonzekera cha PRP ndipo chingakhale ndi kusiyana kwakukulu.Pali mikangano yambiri yokhudzana ndi kukhalapo kwa ma leukocyte ndikuthandizira kwawo pazinthu zosiyanasiyana za PRP (monga PRGF, P-PRP, LP-PRP, LR-PRP, P-PRF ndi L-PRF) Mu ndemanga yaposachedwa, zisanu ndi chimodzi mwachisawawa. mayesero olamulidwa (umboni wa 1) ndi maphunziro atatu oyerekeza oyerekeza (umboni mlingo 2) anakhudza odwala 1055, kusonyeza kuti LR-PRP ndi LP-PRP anali ndi chitetezo chofanana.Wolembayo adatsimikiza kuti choyipa cha PRP sichingakhale chokhudzana ndi kuchuluka kwa maselo oyera a magazi.Mu phunziro lina, LR-PRP sinasinthe interleukin yotupa (IL-1) mu OA bondo β, IL-6, IL-8 ndi IL-17).Zotsatirazi zimathandizira lingaliro lakuti ntchito ya leukocyte mu ntchito yachilengedwe ya PRP mu vivo ingabwere kuchokera ku crosstalk pakati pa mapulateleti ndi leukocyte.Kuyanjana kumeneku kungapangitse biosynthesis ya zinthu zina (monga lipoxygen), zomwe zingathe kuthetsa kapena kulimbikitsa kutsika kwa kutupa.Pambuyo pa kutulutsidwa koyambirira kwa mamolekyu otupa (arachidonic acid, leukotriene ndi prostaglandin), lipoxygen A4 imatulutsidwa m'mapulateleti oyendetsedwa kuti ateteze neutrophil activation.Ndi mu chikhalidwe ichi kuti M Φ Phenotype kuchokera ku M Φ 1 Sinthani ku M Φ 2. Kuwonjezera apo, pali umboni wochuluka wosonyeza kuti ma cell a mononuclear ozungulira amatha kusiyanitsa mitundu yosiyanasiyana ya maselo omwe si a phagocytic chifukwa cha kuchuluka kwawo.

Mtundu wa PRP udzakhudza chikhalidwe cha MSC.Poyerekeza ndi zitsanzo zoyera za PRP kapena PPP, LR-PRP ingapangitse kuchulukira kwakukulu kwa mafupa omwe amachokera ku MSCs (BMMSCs), ndi kumasulidwa mofulumira komanso ntchito yabwino ya PGF.Makhalidwe onsewa amathandizira kuwonjezera ma monocyte mu botolo lamankhwala la PRP ndikuzindikira kuthekera kwawo kwa immunomodulatory komanso kuthekera kosiyanitsa.

Congenital and adaptive immune regulation ya PRP

Ntchito yodziwika kwambiri yokhudza thupi ya mapulateleti ndikuwongolera magazi.Iwo kudziunjikira pa minofu kuwonongeka malo ndi kuonongeka mitsempha.Zochitika izi zimachitika chifukwa cha mawu a integrins ndi selectins omwe amalimbikitsa kuphatikizika kwa mapulateleti ndi kuphatikizana.Kuwonongeka kwa endothelium kumawonjezeranso izi, ndipo collagen yowonekera ndi mapuloteni ena a subendothelial matrix amalimbikitsa kuyatsa kwakuya kwa mapulateleti.Pazochitikazi, gawo lofunikira la mgwirizano pakati pa von Willebrand factor (vWF) ndi glycoprotein (GP), makamaka GP-Ib, zatsimikiziridwa.Pambuyo poyambitsa mapulateleti, mapulateleti α-, Dense, lysosome ndi T-granules amawongolera exocytosis ndikutulutsa zomwe zili m'malo opezeka kunja.

Platelet adhesion molekyulu

Kuti timvetsetse bwino ntchito ya PRP m'matenda otupa ndi mapulateleti pakuyankhira kwa chitetezo chamthupi, tiyenera kumvetsetsa momwe ma cell a cell receptors (integrins) ndi ma junction adhesion molecules (JAM) ndi ma cell amathandizira amatha kuyambitsa njira zovuta muchitetezo chamkati komanso chosinthika.

Ma Integrins ndi ma cell adhesion adhesion molecules omwe amapezeka m'maselo osiyanasiyana ndipo amawonetsedwa mochulukira pamapulateleti.Integrins zikuphatikizapo a5b1, a6b1, a2b1 LFA-2, (GPIa/IIa) ndi aIIbb3 (GPIIb/IIIa).Nthawi zambiri, amakhala mumkhalidwe wokhazikika komanso wocheperako.Pambuyo poyambitsa, amasinthira ku chikhalidwe chapamwamba chomangirira ligand.Ma Integrins ali ndi ntchito zosiyanasiyana pamapulateleti ndipo amatenga nawo gawo pakulumikizana kwa mapulateleti okhala ndi mitundu ingapo ya maselo oyera amagazi, ma cell endothelial ndi matrix a extracellular.Kuphatikiza apo, GP-Ib-V-IX zovuta zimawonetsedwa pa membrane wapulateleti ndipo ndiye cholandirira chachikulu chomangirira ndi von vWF.Kulumikizana uku kumayimira kulumikizana koyamba pakati pa mapulateleti ndi zida zowonekera za subendothelial.Platelet integrin ndi GP zovuta zimagwirizana ndi njira zosiyanasiyana zotupa ndipo zimagwira ntchito yofunika kwambiri popanga mapulateleti-leukocyte.Mwachindunji, integrin aIIbb3 ndiyofunika kupanga chokhazikika chokhazikika mwa kuphatikiza fibrinogen ndi macrophage 1 antigen (Mac-1) receptor pa neutrophils.

Mapulateleti, neutrophils ndi vascular endothelial cell amawonetsa ma cell adhesion adhesion, otchedwa selectin.Pazifukwa zotupa, mapulateleti amawonetsa P-selectin ndi neutrophil L-selectin.Pambuyo poyambitsa mapulateleti, P-selectin ikhoza kumangirira ku ligand PSGL-1 yomwe ilipo pa neutrophils ndi monocytes.Kuphatikiza apo, kumangiriza kwa PSGL-1 kumayambitsa ma intracellular signal cascade reaction, yomwe imayambitsa ma neutrophils kudzera mu neutrophil integrin Mac-1 ndi lymphocyte function-related antigen 1 (LFA-1).Adamulowetsa Mac-1 amamanga kwa GPIb kapena GPIIb/IIIa pa mapulateleti kudzera fibrinogen, motero kukhazikika mogwirizana pakati neutrophils ndi mapulateleti.Komanso, adamulowetsa LFA-1 akhoza kuphatikiza ndi kupatsidwa zinthu za m`mwazi intercellular adhesion molekyulu 2 kupititsa patsogolo bata neutrophil-platelet complex kulimbikitsa adhesion yaitali ndi maselo.

Mapulateleti ndi ma leukocyte amagwira ntchito yofunika kwambiri pakuyankha kwachibadwa komanso kusinthika kwa chitetezo chamthupi

Thupi limatha kuzindikira matupi akunja ndi minyewa yovulala mu matenda owopsa kapena osatha kuti ayambitse kuchiritsa kwa mabala komanso njira yotupa.Chitetezo chobadwa nacho komanso chosinthika chimateteza wolandirayo ku matenda, ndipo maselo oyera amagazi amagwira ntchito yofunika kwambiri pakulumikizana pakati pa machitidwe awiriwa.Mwachindunji, ma monocytes, macrophages, neutrophils ndi maselo akupha achilengedwe amagwira ntchito yofunika kwambiri m'thupi lachibadwa, pamene ma lymphocyte ndi ma subsets awo amagwira ntchito yofanana ndi chitetezo cha mthupi.

Kuyanjana kwa Platelet ndi leukocyte mu kuyanjana kwa maselo amkati a chitetezo chamthupi.Platelet imagwirizana ndi neutrophils ndi monocytes, ndipo potsiriza ndi M Φ Interact, kusintha ndi kuonjezera ntchito zawo.Kuyanjana kwa mapulateleti-leukocyte kumabweretsa kutupa kudzera munjira zosiyanasiyana, kuphatikiza NETosis.Mafupipafupi: MPO: myeloperoxidase, ROS: mitundu ya okosijeni yokhazikika, TF: minofu factor, NET: neutrophil extracellular trap, NF- κ B: Nuclear factor kappa B, M Φ: Macrophages.

Chitetezo chobadwa nacho

Ntchito ya chitetezo cham'thupi ndikuzindikira tizilombo toyambitsa matenda kapena tizidutswa ta minofu ndikuwapangitsa kuti atuluke.Mapangidwe ena a mamolekyu otchedwa surface expression pattern recognition receptors (PRRs) akaphatikizana ndi mamolekyu okhudzana ndi tizilombo toyambitsa matenda komanso mamolekyu okhudzana ndi kuwonongeka, chitetezo chamthupi chobadwa nacho chidzayatsidwa.Pali mitundu yambiri ya ma PRR, kuphatikiza Toll-like receptor (TLR) ndi RIG-1 ngati receptor (RLR).Ma receptor awa amatha kuyambitsa chinthu chachikulu cholembera kappa B (NF- κ B) Imayang'aniranso mbali zingapo zakuyankha kwachilengedwe komanso kusinthika kwa chitetezo chamthupi.Chochititsa chidwi n'chakuti mapulateleti amasonyezanso mitundu yosiyanasiyana ya ma immunoregulatory receptor molecules pamwamba pawo ndi cytoplasm, monga P-selectin, transmembrane protein CD40 ligand (CD40L), ma cytokines (monga IL-1 β, TGF- β) Ndi mapulateleti enieni TRL. Chifukwa chake, mapulateleti amatha kulumikizana ndi maselo osiyanasiyana oteteza thupi.

Kulumikizana kwa maselo oyera a Platelet mu chitetezo chamthupi

Mapulateleti akalowa kapena kulowa m'magazi kapena minofu, mapulateleti ndi amodzi mwa maselo omwe amazindikira kuvulala kwa endothelial ndi tizilombo toyambitsa matenda poyamba.Kuphatikizika kwa mapulateleti ndikulimbikitsa kutulutsidwa kwa mapulateleti agonists ADP, thrombin ndi vWF, zomwe zimapangitsa kuti mapulateleti ayambe kugwira ntchito komanso kuwonetsa mapulateleti a chemokine receptors C, CC, CXC ndi CX3C, motero kumayambitsa mapulateleti pamalo omwe ali ndi kachilombo kapena kuvulala.

Chitetezo cha m'thupi mwachibadwa chimakonzedweratu kuti chizindikire oukira, monga mavairasi, mabakiteriya, tizilombo toyambitsa matenda ndi poizoni, kapena mabala a minofu ndi zilonda.Ndi dongosolo losakhala lachindunji, chifukwa tizilombo toyambitsa matenda tidzadziwika kuti ndi achilendo kapena osakhala enieni komanso opezeka mwamsanga.Chitetezo cha mthupi chimadalira mapuloteni ndi ma phagocytes, omwe amazindikira mikhalidwe yosungidwa bwino ya tizilombo toyambitsa matenda ndipo imayambitsa mwamsanga chitetezo cha mthupi kuti chithandize kuthetsa owononga, ngakhale ngati wolandirayo sanakumanepo ndi tizilombo toyambitsa matenda.

Neutrophils, monocytes ndi maselo a dendritic ndi maselo a chitetezo chamthupi omwe amapezeka kwambiri m'magazi.Kulemba kwawo ndikofunikira kuti chitetezo chamthupi chitetezeke.Pamene PRP imagwiritsidwa ntchito mu mankhwala obwezeretsanso, kuyanjana kwa maselo oyera a platelet kumayambitsa kutupa, kuchiritsa mabala ndi kukonza minofu.TLR-4 pa mapulateleti amathandizira kuyanjana kwa mapulateleti-neutrophil, omwe amawongolera zomwe zimatchedwa leukocyte oxidative kuphulika mwa kuwongolera kutulutsidwa kwa mitundu yogwira ntchito ya okosijeni (ROS) ndi myeloperoxidase (MPO) kuchokera ku neutrophils.Kuphatikiza apo, kuyanjana pakati pa platelet-neutrophil ndi neutrophil degranulation kumabweretsa kupanga misampha ya neutrophil-extracellular (NETs).NETs amapangidwa ndi neutrophil nucleus ndi zina za neutrophil intracellular, zomwe zimatha kugwira mabakiteriya ndikuwapha kudzera mu NEtosis.Mapangidwe a NETs ndi njira yofunika kwambiri yophera ma neutrophils.

Pambuyo poyambitsa mapulateleti, ma monocyte amatha kusamukira kumagulu odwala komanso osokonekera, komwe amagwira ntchito zomatira ndikutulutsa mamolekyu otupa omwe angasinthe chemotaxis ndi ma proteolytic.Kuonjezera apo, mapulateleti amatha kuchititsa kuti monocyte NF- κ B ayambe kuyendetsa bwino ntchito ya monocytes, yomwe ndi mkhalapakati wofunikira wa kuyankha kwa kutupa ndi kuyambitsa ndi kusiyanitsa kwa maselo a chitetezo cha mthupi.Mapulateleti amalimbikitsanso kuphulika kwa endogenous oxidative ya monocytes kulimbikitsa chiwonongeko cha tizilombo toyambitsa matenda.Kutulutsidwa kwa MPO kumayanjanitsidwa ndi kuyanjana kwachindunji pakati pa ma platelet-monocyte CD40L-MAC-1.Chochititsa chidwi n'chakuti, pamene P-selectin imayambitsa mapulateleti pansi pa zovuta zowonongeka komanso zowonongeka, ma chemokines opangidwa ndi mapulateleti PF4, RANTES, IL-1 β Ndi CXCL-12 amatha kuteteza apoptosis ya monocyte, koma amalimbikitsa kusiyana kwawo mu macrophages.

Adaptive immune system

Chitetezo cha mthupi chikazindikira kuwonongeka kwa tizilombo tating'onoting'ono kapena minyewa, chitetezo chamthupi chokhazikika chidzatenga mphamvu.Machitidwe osinthika amaphatikizapo ma antigen-binding B lymphocytes (B maselo) ndi T lymphocytes (Treg) wamba omwe amagwirizanitsa chilolezo cha tizilombo toyambitsa matenda.Ma cell a T amatha kugawidwa kukhala othandizira T (Th cell) ndi cytotoxic T cell (ma cell Tc, omwe amadziwikanso kuti T killer cell).Maselo a Th1, Th2 ndi Th17 amagawidwanso m'maselo a Th1, omwe ali ndi ntchito zazikulu mu kutupa.Maselo amatha kupanga ma cytokines otupa (monga IFN- γ, TNF- β) Ndi ma interleukins angapo (mwachitsanzo, IL-17) Ndiwothandiza kwambiri poletsa ma virus komanso mabakiteriya. Ma cell a Tc ndi maselo amphamvu, omwe amatha kuthetsa tizilombo toyambitsa matenda komanso ma cell.

Chochititsa chidwi n'chakuti, maselo a Th2 amapanga IL-4 ndipo amakhudza M Φ Polarization, M Φ Kuwongolera kotsogoleredwa M Φ 2 Phenotype, pamene IFN- γ M Φ Kusintha kwa kutupa M Φ 1 Phenotype, zomwe zimadalira mlingo ndi nthawi ya cytokines.Pambuyo pa IL-4, M Φ 2 imapangitsa kuti maselo a Treg asiyanitse m'maselo a Th2, kenako amapanga IL-4 yowonjezera (positive feedback loop).Maselo a Th amatembenuza M Φ The phenotype imayendetsedwa ku regenerative phenotype poyankha ma biological agents a chiyambi cha minofu.Njirayi imachokera ku umboni wakuti maselo a Th amagwira ntchito yofunika kwambiri poletsa kutupa ndi kukonza minofu.

Kulumikizana kwa maselo oyera a Platelet mu chitetezo chokwanira

Chitetezo cha mthupi chimagwiritsa ntchito ma antigen-enieni ma receptor ndipo chimakumbukira tizilombo toyambitsa matenda zomwe tidakumana nazo m'mbuyomu, ndikuziwononga zikakumana ndi wolandirayo.Komabe, mayankho osinthika a chitetezo chamthupi awa adakula pang'onopang'ono.Konias et al.Zimasonyeza kuti chigawo cha platelet chimapangitsa kuti chiwopsezo chizindikire komanso kukonzanso minofu, komanso kuti mgwirizano pakati pa mapulateleti ndi leukocyte umalimbikitsa kuyambitsa kuyankha kwa chitetezo cha mthupi.

Panthawi yosinthika ya chitetezo chamthupi, mapulateleti amalimbikitsa mayankho a monocyte ndi macrophage kudzera pakukula kwa ma cell a DC ndi NK, zomwe zimatsogolera ku mayankho enieni a T cell ndi B cell.Chifukwa chake, zigawo za platelet granule zimakhudza mwachindunji chitetezo chamthupi pofotokoza CD40L, molekyulu yomwe ndiyofunikira pakuwongolera kuyankha kwa chitetezo chamthupi.Mapulateleti kudzera mu CD40L samangokhala ndi gawo pakuwonetsa ma antigen, komanso amakhudza momwe ma cell amachitira.Liu et al.Zinapezeka kuti mapulateleti amawongolera kuyankhidwa kwa maselo a CD4 T m'njira yovuta.Kusiyanitsa kumeneku kwa maselo a CD4 T kumatanthawuza kuti mapulateleti amalimbikitsa maselo a CD4 T kuti agwirizane ndi zoyambitsa zotupa, motero amapanga mayankho amphamvu oletsa kutupa ndi odana ndi kutupa.

Mapulateleti amawongoleranso kuyankha kwa ma cell a B ku tizilombo toyambitsa matenda.Ndizodziwika bwino kuti CD40L pa ma CD4 T omwe atsegulidwa adzayambitsa ma CD40 a B maselo, kupereka chizindikiro chachiwiri chofunika kuti T-cell-dependent B lymphocyte activation, kutembenuka kwa allotype, ndi B cell kusiyana ndi kuchulukana.Kawirikawiri, zotsatira zimasonyeza bwino ntchito zosiyanasiyana za mapulateleti mu chitetezo chokwanira, kusonyeza kuti mapulateleti amagwirizanitsa mgwirizano pakati pa T ndi maselo a B kupyolera mu CD40-CD40L, motero kumapangitsa kuti maselo a B omwe amadalira T-cell.Kuphatikiza apo, mapulateleti ali ndi ma cell a cell receptors, omwe amatha kulimbikitsa kuyambika kwa mapulateleti ndikutulutsa mamolekyu ambiri otupa komanso achilengedwe omwe amasungidwa m'tinthu tating'onoting'ono tapulateleti, motero zimakhudza momwe chitetezo chamthupi chimakhalira komanso chosinthika.

Ntchito yowonjezereka ya serotonin yotengedwa ndi mapulateleti mu PRP

Serotonin (5-hydroxytryptamine, 5-HT) ali ndi udindo womveka bwino m'kati mwa dongosolo la mitsempha (CNS), kuphatikizapo kulekerera kupweteka.Akuti ambiri mwa anthu 5-HT amapangidwa m'matumbo am'mimba ndipo kenako kudzera m'magazi, pomwe amatengedwa ndi mapulateleti kudzera mu serotonin reuptake transporter ndikusungidwa mu tinthu tating'ono kwambiri (65 mmol / L).5-HT ndi neurotransmitter yodziwika bwino komanso mahomoni omwe amathandiza kuwongolera njira zosiyanasiyana za neuropsychological mu CNS (chapakati 5-HT).Komabe, zambiri za 5-HT zimakhalapo kunja kwa CNS (zotumphukira 5-HT), ndipo zimakhudzidwa ndi kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe kake, kuphatikizapo mtima, mapapo, m'mimba, urogenital ndi platelet.5-HT ili ndi kagayidwe kamene kamadalira ndende pamitundu yosiyanasiyana ya maselo, kuphatikizapo adipocytes, maselo a epithelial ndi maselo oyera a magazi.Peripheral 5-HT imakhalanso ndi mphamvu yoteteza chitetezo cha mthupi, yomwe imatha kulimbikitsa kapena kuletsa kutupa ndikukhudza maselo osiyanasiyana a chitetezo cha mthupi kudzera mu 5-HT receptor (5HTR).

Njira ya Paracrine ndi autocrine ya HT

Ntchito ya 5-HT imayanjanitsidwa ndi kuyanjana kwake ndi 5HTRs, yomwe ndi banja lapamwamba lomwe lili ndi mamembala asanu ndi awiri (5-HT 1 - 7) komanso osachepera 14 osiyana siyana olandirira, kuphatikizapo membala yemwe wapezeka posachedwapa 5-HT 7, zotumphukira zake ndi ntchito mu kasamalidwe ululu.M'kati mwa kusungunuka kwa mapulateleti, mapulateleti ogwiritsidwa ntchito amatulutsa chiwerengero chachikulu cha 5-HT chochokera ku platelet, chomwe chingapangitse kuti mitsempha ya mitsempha ikhale yowonjezereka komanso imapangitsa kuti mapulateleti oyandikana nawo ndi ma lymphocyte ayambe mwa kufotokoza kwa 5-HTR pa maselo a endothelial, maselo osalala a minofu ndi ma lymphocyte. maselo oteteza thupi.Pacala et al.Zotsatira za mitotic za 5-HT pa maselo a vascular endothelial anaphunziridwa, ndipo kuthekera kwa kulimbikitsa kukula kwa mitsempha yowonongeka mwa kulimbikitsa angiogenesis kunatsimikiziridwa.Momwe njirazi zimagwiritsidwira ntchito sizidziwika bwino, koma zingaphatikizepo kusiyanitsa njira ziwiri zowonetsera njira mu minofu ya microcircuit kuti iwonetsetse ntchito za maselo a mitsempha ya endothelial ndi maselo osalala a minofu, ma fibroblasts ndi maselo a chitetezo cha mthupi kudzera mwapadera 5-HT zolandilira pa maselowa. .Ntchito ya autocrine ya mapulateleti 5-HT pambuyo poyambitsa mapulateleti yafotokozedwa [REF].Kutulutsidwa kwa 5-HT kumathandizira kutsegulira kwa mapulateleti ndikulembanso mapulateleti ozungulira, zomwe zimatsogolera ku mayendedwe azizindikiro zazizindikiro ndi zotuluka m'mwamba zomwe zimathandizira kuyambiranso kwa mapulateleti.

Immunomodulatory 5-HT zotsatira

Umboni wochulukirachulukira ukuwonetsa kuti serotonin imatha kukhala ndi gawo mu 5HTR yosiyana ngati modulator ya chitetezo.Malinga ndi 5HTR yofotokozedwa m'magulu osiyanasiyana a leukocyte omwe amakhudzidwa ndi kutupa, 5-HT yochokera ku platelet imagwira ntchito ngati chitetezo chamthupi m'thupi lachibadwa komanso lokhazikika.5-HT ikhoza kulimbikitsa kuchuluka kwa Treg ndikuwongolera ntchito za maselo a B, maselo akupha zachilengedwe ndi neutrophils polemba DC ndi monocytes kumalo otupa.Kafukufuku waposachedwapa wasonyeza kuti 5-HT yopangidwa ndi mapulateleti imatha kuyendetsa ntchito ya maselo a chitetezo cha mthupi pazochitika zinazake.Choncho, pogwiritsa ntchito C-PRP, chiwerengero cha platelet ndi chachikulu kuposa 1 × 10 6 / µ L chingathandize kwambiri kunyamula 5-HT yochokera ku mapulateleti akuluakulu kupita ku minofu.Mu chilengedwe chodziwika ndi zigawo zowonongeka, PRP ikhoza kuyanjana ndi maselo angapo a chitetezo cha mthupi omwe amagwira ntchito yofunika kwambiri m'matendawa, omwe angakhudze zotsatira zachipatala.

Chithunzi chosonyeza kuyankha kosiyanasiyana kwa 5-HT pambuyo poyambitsa mapulateleti otupa a PRP.Pambuyo poyambitsa mapulateleti, mapulateleti amamasula ma granules awo, kuphatikizapo 5-HT mu granules wandiweyani, omwe ali ndi zotsatira zosiyana siyana pamagulu osiyanasiyana a chitetezo cha mthupi, maselo a endothelial ndi maselo osalala a minofu.Mafupipafupi: SMC: maselo osalala a minofu, EC: maselo a endothelial, Treg: T lymphocytes ochiritsira, M Φ: Macrophages, DC: maselo a dendritic, IL: interleukin, IFN- γ: Interferon γ. Kusinthidwa ndi kusinthidwa kuchokera ku Everts et al.ndi Hull et al.

Analgesic zotsatira za PRP

Mapulateleti ogwiritsidwa ntchito amamasula oyimira pakati omwe amathandizira-kutupa komanso odana ndi kutupa, omwe sangangoyambitsa ululu, komanso amachepetsa kutupa ndi kupweteka.Akagwiritsidwa ntchito, mphamvu ya mapulateleti ya PRP imasintha microenvironment isanayambe kukonzanso minofu ndi kusinthika kudzera m'njira zosiyanasiyana zovuta zokhudzana ndi anabolism ndi catabolism, kuchuluka kwa maselo, kusiyanitsa ndi kulamulira maselo a stem.Makhalidwewa a PRP amachititsa kuti PRP igwiritsidwe ntchito muzochitika zosiyanasiyana zachipatala zomwe nthawi zambiri zimagwirizanitsidwa ndi ululu wosatha (monga kuvulala kwa masewera, matenda a mafupa, matenda a msana ndi chilonda chovuta kwambiri), ngakhale kuti njira yeniyeniyo sinatsimikizidwe mokwanira.

Mu 2008, Evertz et al.Ndilo kuyesa koyamba kosasinthika kuti afotokoze zotsatira za analgesic za kukonzekera kwa PRP, zomwe zimakonzedwa kuchokera ku bulauni wosanjikiza wa autologous erythrocyte sedimentation rate ndikuyambitsa ndi autologous thrombin pambuyo pa opaleshoni yamapewa.Iwo adawona kuchepa kwakukulu kwa mawonedwe a analogue sikelo, kugwiritsa ntchito ma analgesics opioid, komanso kukonzanso bwino pambuyo pa opaleshoni.Ndizofunikira kudziwa kuti amawonetsa mphamvu ya analgesic ya mapulateleti otsegulidwa ndikulingalira za momwe mapulateleti akutulutsa 5-HT.Mwachidule, mapulateleti ali ogona mu PRP yokonzedwa kumene.Pambuyo poyambitsa mapulateleti mwachindunji kapena mwanjira ina (tishu), mapulateleti amasintha mawonekedwe ndikupanga zabodza kuti alimbikitse kuphatikizika kwa mapulateleti.Kenako, amamasula ma intracellular α- Ndipo wandiweyani particles.Minofu yothandizidwa ndi PRP yoyendetsedwa idzalowetsedwa ndi PGF, ma cytokines ndi ma lysosomes ena a platelet.Makamaka, pamene tinthu tating'onoting'ono timatulutsa zomwe zili mkati mwake, zimamasula kuchuluka kwa 5-HT komwe kumayang'anira ululu.Mu C-PRP, kuchuluka kwa mapulateleti ndi 5 mpaka 7 nthawi zambiri kuposa m'magazi ozungulira.Chifukwa chake, kutulutsidwa kwa 5-HT kuchokera ku mapulateleti ndikokwanira zakuthambo.Chochititsa chidwi, Sprott et al.Lipotilo linawona kuti ululu unatsitsimutsidwa kwambiri pambuyo pa acupuncture ndi moxibustion, chiwerengero cha platelet chochokera ku 5-HT chinachepetsedwa kwambiri, ndiyeno mlingo wa plasma wa 5-HT unawonjezeka.

Kumbali, mapulateleti, mast cell ndi endothelial cell adzatulutsa endogenous 5-HT panthawi ya kuvulala kwa minofu kapena kuvulala kwa opaleshoni.Chochititsa chidwi n'chakuti, mitundu yosiyanasiyana ya 5-HT yolandirira ma neuroni inapezeka m'madera ozungulira, omwe amatsimikizira kuti 5-HT ikhoza kusokoneza kufalikira kwa nociceptive kumalo ozungulira.Kafukufukuyu akuwonetsa kuti 5-HT ingakhudze kutumiza kwa nociceptive kwa minyewa yam'mphepete mwa 5-HT1, 5-HT2, 5-HT3, 5-HT4 ndi 5-HT7 receptors.

Dongosolo la 5-HT limayimira dongosolo lamphamvu lomwe lingachepetse ndikuwonjezera kuchuluka kwa zowawa pambuyo pakukondoweza kovulaza.Malamulo apakati ndi ozungulira a zizindikiro za nociceptive ndi kusintha kwa dongosolo la 5-HT zanenedwa kwa odwala omwe ali ndi ululu wosatha.M'zaka zaposachedwa, kafukufuku wambiri amayang'ana kwambiri ntchito ya 5-HT ndi zolandilira zake pakukonza ndikuwongolera zidziwitso zovulaza, zomwe zimapangitsa kuti pakhale mankhwala monga selective serotonin reuptake inhibitors (SSRI).Mankhwalawa amalepheretsa kubwezeretsanso kwa serotonin mu presynaptic neurons pambuyo pa kutulutsidwa kwa serotonin.Zimakhudza nthawi komanso mphamvu ya kulankhulana kwa serotonin ndipo ndi njira ina yothandizira ululu wosatha.Kufufuza kwina kwachipatala kumafunika kuti mumvetse bwino njira ya maselo a PRP-derived 5-HT kupweteka kwa matenda mu matenda aakulu ndi owonongeka.

Deta ina yothetsera vuto la analgesic la PRP lingapezeke pambuyo pa kuyesa kwachitsanzo cha nyama ya analgesic.Zowerengera zofananira mumitundu iyi ndizovuta chifukwa maphunzirowa ali ndi mitundu yambiri.Komabe, maphunziro ena azachipatala afotokoza za nociceptive ndi analgesic zotsatira za PRP.Kafukufuku wambiri wasonyeza kuti odwala omwe akulandira chithandizo cha tendinosis kapena misozi ya rotator sakhala ndi ululu wochepa.Mosiyana ndi zimenezi, maphunziro ena angapo asonyeza kuti PRP ikhoza kuchepetsa kapena kuthetsa ululu wa odwala omwe ali ndi vuto la tendon, OA, plantar fasciitis ndi matenda ena a phazi ndi akakolo.Kuphatikizika komaliza kwa mapulateleti ndi ma cell cell achilengedwe zadziwika kuti ndizofunika kwambiri za PRP, zomwe zimathandiza kuwona zotsatira zokhazikika za analgesic pambuyo pa kugwiritsa ntchito PRP.Zosintha zina zimaphatikizapo njira yoperekera PRP, teknoloji yogwiritsira ntchito, platelet activation protocol, biological activity level of PGF ndi cytokines yotulutsidwa, mtundu wa minofu ya PRP application ndi mtundu wovulaza.

N'zochititsa chidwi kuti Kuffler anathetsa kuthekera kwa PRP pochepetsa ululu kwa odwala omwe ali ndi ululu wochepa kwambiri waumphawi waumphawi, wachiwiri kwa mitsempha yowonongeka yosasinthika.Cholinga cha phunziroli ndikufufuza ngati ululu wa neuropathic ukhoza kuchepetsedwa kapena kuchepetsedwa chifukwa cha PRP kulimbikitsa kusinthika kwa axonal ndi kubwezeretsanso mitsempha.Chodabwitsa n'chakuti pakati pa odwala omwe akulandira chithandizo, ululu wa neuropathic umachotsedwabe kapena kuchepetsedwa osachepera zaka zisanu ndi chimodzi pambuyo pa opaleshoni.Kuonjezera apo, odwala onse anayamba kuthetsa ululu mkati mwa masabata atatu atagwiritsa ntchito PRP.

Posachedwapa, zotsatira zofananira za PRP za analgesic zawonedwa m'munda wa bala pambuyo pa opaleshoni ndi chisamaliro cha khungu.Chochititsa chidwi n'chakuti, olembawo anafotokoza za thupi la ululu wa bala wokhudzana ndi kuvulala kwa mitsempha ndi hypoxia ya khungu.Adakambirananso za kufunika kwa angiogenesis pakuwongolera oxygenation ndikupereka michere.Kafukufuku wawo adawonetsa kuti poyerekeza ndi gulu lolamulira, odwala omwe amalandila chithandizo cha PRP anali ndi zowawa zochepa komanso kuchuluka kwa angiogenesis.Potsirizira pake, Johal ndi anzake adachita ndondomeko yowonongeka ndi kusanthula meta ndipo adatsimikiza kuti PRP ikhoza kuchepetsa ululu pambuyo pogwiritsira ntchito PRP mu zizindikiro za mafupa, makamaka kwa odwala omwe amalandira chithandizo cha epicondylitis kunja ndi mawondo OA.Tsoka ilo, phunziroli silinatchule zotsatira za maselo oyera a magazi, kuchuluka kwa mapulateleti kapena kugwiritsa ntchito ma exogenous platelet activator, chifukwa zosinthazi zingakhudze mphamvu yonse ya PRP.Kuchuluka kwa mapulateleti a PRP kuti muchepetse kupweteka kwambiri sikudziwika bwino.Mu chitsanzo cha makoswe a tendinosis, chiwerengero cha platelet chinali 1.0 × 10 6 / μ Pa L, ululu ukhoza kuthetsedwa kwathunthu, pamene kupweteka kwa PRP ndi theka la chiwerengero cha platelet kumachepetsedwa kwambiri.Choncho, timalimbikitsa maphunziro ambiri azachipatala kuti afufuze zotsatira za analgesic za kukonzekera kosiyana kwa PRP.

PRP ndi angiogenesis effect

Kukonzekera kwa C-PRP mumankhwala enieni obwezeretsanso amalola kutulutsa ma biomolecules otulutsidwa ndi kuchuluka kwa mapulateleti omwe amatsegulidwa pamasamba omwe amatsata.Chifukwa chake, machitidwe osiyanasiyana a cascade adayambika, omwe amathandizira pakuwongolera chitetezo chamthupi, njira yotupa komanso angiogenesis kulimbikitsa machiritso ndi kukonza minofu.

Angiogenesis ndi njira yosunthika yomwe imaphatikizapo kumera ndi timinofu tating'onoting'ono kuchokera m'mitsempha yomwe inalipo kale.Angiogenesis yapita patsogolo chifukwa cha njira zosiyanasiyana zamoyo, kuphatikizapo endothelial cell migration, kuchulukana, kusiyanitsa ndi kugawa.Njira zama cell izi ndizofunikira pakupanga mitsempha yatsopano yamagazi.Ndiwofunikira pakukulitsa kwa mitsempha yamagazi yomwe idalipo kale kuti ibwezeretse kuyenda kwa magazi komanso kuthandizira kagayidwe kachakudya kakukonzanso kwa minofu ndi kusinthika kwa minofu.Mitsempha yamagazi yatsopanoyi imalola kutulutsa mpweya ndi michere, komanso kuchotsedwa kwa zinthu zina kuchokera kumagulu ochiritsidwa.

Ntchito ya angiogenesis imayendetsedwa ndi zolimbikitsa za angiogenic factor VEGF ndi anti-angiogenic factor (mwachitsanzo, angiostatin ndi thrombospondin-1 [TSP-1]).M'malo omwe ali ndi matenda komanso owonongeka (kuphatikiza kuchepa kwa oxygen, kutsika kwa pH ndi kuchuluka kwa lactic acid), zinthu zam'deralo za angiogenic zidzabwezeretsa ntchito ya angiogenesis.

Magulu angapo osungunuka a mapulateleti, monga FGF ndi TGF- β Ndipo VEGF imatha kulimbikitsa ma cell a endothelial kupanga mitsempha yatsopano yamagazi.Landsdown ndi Fortier adanenanso zotsatira zosiyanasiyana zokhudzana ndi kapangidwe ka PRP, kuphatikiza magwero a intraplatelet a owongolera ambiri angiogenic.Kuonjezera apo, adatsimikiza kuti kuwonjezeka kwa angiogenesis kumathandizira kuchiza matenda a MSK m'madera omwe ali ndi vuto la vascularization, monga meniscus misozi, kuvulala kwa tendon ndi madera ena omwe ali ndi vuto la vascularization.

Kupititsa patsogolo ndi anti-angiogenic platelet properties

M'zaka makumi angapo zapitazi, kafukufuku wofalitsidwa watsimikizira kuti mapulateleti amagwira ntchito yofunika kwambiri mu hemostasis yoyamba, kupangika kwa magazi, kukula kwa kukula ndi kutulutsidwa kwa cytokine, ndi kulamulira kwa angiogenesis monga gawo la kukonzanso minofu.Chodabwitsa, PRP α- Ma granules ali ndi zida za pro-angiogenic kukula, mapuloteni odana ndi angiogenic ndi ma cytokines (monga PF4, plasminogen activator inhibitor-1 ndi TSP-1), ndipo amayang'ana kutulutsa zinthu zina zomwe zimagwira ntchito. .Ntchito mu angiogenesis.Choncho, ntchito ya PRP poyang'anira angiogenesis regulation ingatanthauzidwe ndi kutsegulira kwa maselo enieni a maselo, TGF- β Yambani machitidwe a pro-angiogenic ndi anti-angiogenic.Kuthekera kwa mapulateleti kuchita njira ya angiogenesis kwatsimikiziridwa mu pathological angiogenesis ndi chotupa angiogenesis.

Platelet-derived angiogenic growth factor and anti-angiogenic growth factor, yochokera ku α- Ndipo wandiweyani ndi zomatira mamolekyu.Chofunika kwambiri, ndizovomerezeka kuti mphamvu yonse ya mapulateleti pa angiogenesis ndi pro-angiogenic ndi stimulating.Zikuyembekezeka kuti chithandizo cha PRP chidzalamulira kulowetsedwa kwa angiogenesis, zomwe zidzathandiza kuti pakhale chithandizo cha matenda ambiri, monga machiritso a zilonda ndi kukonza minofu.Ulamuliro wa PRP, makamaka kasamalidwe kapamwamba ka PGF ndi ma cytokines ena a platelet, angapangitse angiogenesis, angiogenesis ndi arteriogenesis, chifukwa stromal cell-derived factor 1a imamangiriza ku CXCR4 receptor pa endothelial progenitor cell.Bill ndi al.Akuti PRP imakulitsa ischemic neovascularization, yomwe ingakhale chifukwa cha kukondoweza kwa angiogenesis, angiogenesis ndi arteriogenesis.Mu mtundu wawo wa in vitro, kuchuluka kwa ma cell a endothelial ndi mapangidwe a capillary kudapangidwa ndi kuchuluka kwa ma PDG osiyanasiyana, pomwe VEGF inali stimulator yayikulu ya angiogenic.Chinthu china chofunikira komanso chofunikira pakubwezeretsa njira ya angiogenesis ndi mgwirizano pakati pa ma PGF angapo.Richardson et al.Zinatsimikiziridwa kuti synergistic ntchito ya angiogenic factor platelet-derived growth factor-bb (PDGF-BB) ndi VEGF inachititsa kuti pakhale mapangidwe okhwima a mitsempha ya mitsempha poyerekeza ndi ntchito ya kukula kwa munthu.Kuphatikizika kwa zinthu izi posachedwapa kunatsimikiziridwa mu kafukufuku wokhudza kupititsa patsogolo kayendedwe ka ubongo mu mbewa ndi hypoperfusion ya nthawi yayitali.

Chofunika kwambiri, kafukufuku wa in vitro anayeza kuchuluka kwa ma cell a umbilical vein endothelial cell komanso kuchuluka kwa mapulateleti posankha chipangizo chokonzekera cha PRP ndi njira ya mlingo wa kupatsidwa zinthu za m'mwazi, ndipo zotsatira zake zinasonyeza kuti mlingo woyenera wa kupatsidwa zinthu za m'mwazi unali 1.5 × 10 6 mapulateleti/ μ. 50. Kulimbikitsa angiogenesis.Kuchulukirachulukira kwa mapulateleti kumatha kulepheretsa njira ya angiogenesis, motero zotsatira zake zimakhala zoyipa.

Kukalamba kwa ma cell, kukalamba ndi PRP

Ma cell senescence amatha kuyambitsidwa ndi zinthu zosiyanasiyana.Iyi ndi njira yomwe maselo amasiya kugawanika ndikusintha kusintha kwapadera kwa phenotypic kuti ateteze kukula kosalekeza kwa maselo owonongeka, omwe amathandiza kwambiri kupewa khansa.M'kati mwa ukalamba wakuthupi, kukalamba kobwerezabwereza kwa maselo kumalimbikitsanso kukalamba kwa ma cell, ndipo kuthekera kosinthika kwa ma MSC kudzachepetsedwa.

Zotsatira za kukalamba ndi kukalamba kwa maselo

Mu vivo, mitundu yambiri ya maselo imakalamba ndikudziunjikira m'magulu osiyanasiyana akamakalamba, pomwe pali maselo ambiri okalamba.Kuchulukana kwa maselo okalamba kumawoneka kuti kukuwonjezeka ndi kukula kwa zaka, kuwonongeka kwa chitetezo cha mthupi, kuwonongeka kwa minofu kapena zinthu zokhudzana ndi nkhawa.Njira ya ukalamba wa ma cell yadziwika kuti ndi matenda okhudzana ndi zaka, monga osteoarthritis, osteoporosis ndi intervertebral disc degeneration.Zolimbikitsa zosiyanasiyana zimakulitsa ukalamba wa maselo.Poyankha, senescence-related secretory phenotype (SASP) idzatulutsa kuchuluka kwa mapuloteni ndi ma cytokines.Phenotype yapaderayi imakhudzana ndi maselo okalamba, momwe amapangira ma cytokines otupa (monga IL-1, IL-6, IL-8), zinthu zakukula (monga TGF- β, HGF, VEGF, PDGF), MMP, ndi cathepsin.Poyerekeza ndi achinyamata, SAPS yatsimikiziridwa kuti ikuwonjezeka ndi zaka, chifukwa ndondomeko yokhazikika imawonongeka, zomwe zimapangitsa kuti maselo azikalamba komanso kuchepetsa kubadwanso kwatsopano.Makamaka, mu matenda a mafupa ndi matenda a chigoba cha minofu.Pachifukwa ichi, kukalamba kwa chitetezo cha mthupi kumaonedwa kuti ndi kusintha kwakukulu kwa katulutsidwe ka maselo a chitetezo cha mthupi, kusonyeza kuti kuchuluka kwa TNF-a, IL-6 ndi / kapena Il-1b kumawonjezeka, zomwe zimayambitsa kutupa kosatha.Ndikoyenera kudziwa kuti kusokonezeka kwa maselo a stem kumagwirizananso ndi njira zopanda ma cell zodziyimira pawokha, monga maselo okalamba, makamaka kupanga zinthu zoyambitsa kutupa komanso zotsutsana ndi SASP.

M'malo mwake, SASP imathanso kulimbikitsa ma cell plasticity ndikukonzanso ma cell oyandikana nawo.Kuphatikiza apo, SASP ikhoza kulinganiza kuyankhulana ndi oyimira chitetezo osiyanasiyana ndikuyambitsa ma cell achitetezo kuti apititse patsogolo kuchotsedwa kwa maselo okalamba.Kumvetsetsa udindo ndi ntchito ya maselo okalamba kudzathandizira kuchiritsa ndi kukonzanso minofu ya minofu ya MSK ndi mabala aakulu.

Ndizofunikira kudziwa kuti Ritcka et al.Kafukufuku wambiri adachitika, ndipo gawo lalikulu komanso lopindulitsa la SASP polimbikitsa mapulasitiki a cell ndi kusinthika kwa minofu idapezeka, ndipo lingaliro la chithandizo chanthawi yayitali cha maselo okalamba adayambitsidwa.Iwo anatchula mosamala kuti ukalamba makamaka ndi njira yopindulitsa ndi yobwezeretsa.

Kukalamba kwa ma cell ndi kuthekera kwa PRP

Pamene chiwerengero cha tsinde chimachepa, kukalamba kudzakhudza kugwira ntchito kwa maselo a tsinde.Mofananamo, mwa anthu, makhalidwe a tsinde (monga kuuma, kuchulukana ndi kusiyana) amachepetsanso ndi zaka.Wang ndi Nirmala adanenanso kuti kukalamba kungachepetse mawonekedwe a ma cell stem cell komanso kuchuluka kwa zolandilira zomwe zimakula.Kafukufuku wa nyama adawonetsa kuti kuchuluka kwa PDGF mu akavalo achichepere kunali kwakukulu.Iwo adatsimikiza kuti kuwonjezeka kwa chiwerengero cha ma GF receptors ndi chiwerengero cha GF mwa achinyamata akhoza kukhala ndi mayankho abwino a ma cell ku chithandizo cha PRP kusiyana ndi okalamba mwa achinyamata.Zotsatirazi zimasonyeza chifukwa chake chithandizo cha PRP chingakhale chopanda mphamvu kapena chopanda mphamvu kwa odwala okalamba omwe ali ndi maselo ochepa komanso "osauka".Zatsimikiziridwa kuti ukalamba wa ukalamba wa cartilage umasinthidwa ndipo nthawi yopuma ya chondrocytes ikuwonjezeka pambuyo pa jekeseni wa PRP.Jia et al.Amagwiritsidwa ntchito pophunzira mbewa dermal fibroblasts mu vitro photoaging, popanda komanso popanda chithandizo cha PRP, kuti afotokoze bwino momwe PGF counteraction mu chitsanzo ichi.Gulu la PRP linawonetsa zotsatira zachindunji pa matrix a extracellular, kuwonjezeka kwa mtundu wa I collagen ndikuchepetsa kaphatikizidwe ka metalloproteinases, kusonyeza kuti PRP ikhoza kulimbana ndi ukalamba wa maselo, komanso mu matenda osokonekera a MSK.

Mu kafukufuku wina, PRP idagwiritsidwa ntchito kusonkhanitsa maselo okalamba a m'mafupa kuchokera ku mbewa zakale.Zatsimikiziridwa kuti PRP ikhoza kubwezeretsanso ntchito zosiyanasiyana za stem cell kuchokera ku ukalamba, monga kuchuluka kwa maselo ndi mapangidwe a koloni, ndikumanganso zizindikiro zokhudzana ndi ukalamba wa maselo.

Posachedwapa, Oberlohr ndi anzake adaphunzira kwambiri ntchito ya ukalamba wa maselo pakufooketsa kusinthika kwa minofu, ndikuwunika PRP ndi plasma-poor plasma (PPP) monga njira zochiritsira zamoyo zowonongeka kwa chigoba.Iwo ankawona kuti PRP kapena PPP chithandizo cha kukonzanso minofu ya chigoba chidzakhazikitsidwa ndi zinthu zamoyo zomwe zimapangidwira SASP zolembera ma cell ndi zinthu zina zomwe zimabweretsa kukula kwa fibrosis.

Ndizomveka kukhulupirira kuti musanayambe kugwiritsa ntchito PRP, kukalamba kwa maselo omwe akukhudzidwa kungathe kusintha makhalidwe osinthika a chithandizo chamankhwala mwa kuchepetsa zinthu za SASP.Zanenedwa kuti njira ina yowonjezera zotsatira za PRP ndi PPP chithandizo cha kusinthika kwa minofu ya chigoba ndikusankha kuchotsa maselo okalamba ndi okalamba okalamba.Palibe kukayikira kuti zotsatira za kafukufuku waposachedwapa pa zotsatira za PRP pa ukalamba wa maselo ndi ukalamba ndizosangalatsa, koma akadali pachiyambi.Chifukwa chake, sikuli kwanzeru kupanga malingaliro aliwonse panthawi ino.

(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.）