Na Cocer Peptides 
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INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Amakuru Yibanze Yerekeye KPV
KPV ni tripeptide ifite akamaro gakomeye ko kurwanya inflammatory, ituma igira uruhare mubice byinshi.
Igicapo 1 Ingaruka zo kuvura za HA-KPV-NPs kurwanya UC Ubuyobozi bwo mu kanwa bwa HA-KPV-NPs bwinjijwe muri hydrogel (chitosan / alginate) butanga ingaruka zo kuvura kurwanya UC byihutisha gukira kwa mucosa no kugabanya uburibwe.
Uburyo bwo kurwanya inflammatory ya KPV
1. Amabwiriza yinzira zerekana ibimenyetso
NF-κB Inzira Yerekana Inzira: NF-κB nikintu cyingenzi cyo kwandukura kigira uruhare runini mubisubizo byumuriro. Iyo selile zihuye nibitera imbaraga, NF-κB ihinduranya kuva cytoplazme ikajya muri nucleus, igatangira kwandukura ingirabuzimafatizo ya cytokine. KPV irashobora guhagarika ibikorwa bya NF-κB. Mu mara yo mu mara ya epithelia yumuntu hamwe na selile T yumuntu, selile zashishikarijwe na cytokine itera umuriro, kandi KPV yongerwa icyarimwe. Hifashishijwe uburyo nka NF-κB luciferase umunyamakuru wa gene avuga, immunoblotting ya protein, igihe nyacyo cyo guhinduranya transcript polymerase, hamwe na enzyme ihujwe na immunosorbent assay (ELISA), byagaragaye ko KPV yibanda kuri nanomolar ishobora kubuza gukora NF-κB, bityo bikagabanya ururenda rwa cytokine. Ubu buryo ni ingenzi cyane mu kugenzura ibibyimba byo mu mara, kubera ko gukora cyane NF-κB mu ngirabuzimafatizo zo mu nda no mu ngirabuzimafatizo z'umubiri ari ikintu cy'ingenzi kiranga indwara zifata amara (IBD) n'izindi ndwara zifata amara.
MAP kinase yerekana inzira: Mitogen-ikora protein kinase (MAPK) inzira yerekana inzira nindi nzira yingenzi igenga ibisubizo byokongoka, harimo ibimenyetso bidasanzwe bigengwa na kinase (ERK), c-Jun N-terminal kinase (JNK), na p38 MAPK. Izi kinase zikora mugihe selile zihuye nibitera umuriro, biganisha kuri fosifora yibintu byandikirwa hasi kandi bigatera imbere kwerekana genes zijyanye no gutwika. KPV irashobora kandi kubuza MAP kinase inflammatory signal inzira. Iyo selile zihuye nibitera umuriro, KPV irashobora guhagarika ibikorwa bya MAPK, bikagabanya fosifora yibintu byandikirwa hasi, bityo bikagabanya umusaruro wa cytokine itera umuriro. Muburyo bwo gutwika, gukora p38 MAPK biganisha ku kongera imvugo ya cytokine itera inflammatory nka TNF-α na IL-6, mugihe KPV ishobora guhagarika ibikorwa bya p38 MAPK, bikagabanya ururenda rwa cytokine bityo bikagabanya igisubizo cyakongejwe.
2. Ingaruka zo gutwara abantu-selile
Abatwara PepT1: PepT1 ni di / tripeptide itwara abantu ikunze kugaragara mu mara mato ariko ikinjizwa mu mara mugihe cya IBD. Ingaruka zo kurwanya inflammatory ya KPV zahujwe igice na PepT1. Mu bushakashatsi bwa uptake, ubukonje bwa KPV bwakoreshejwe nkibikoresho byo guhatanira irushanwa rya hPepT1 nka radioaktiw yanditseho substrate, cyangwa [⊃3; H] KPV yakoreshejwe kugirango hamenyekane ibimenyetso biranga KPV. KPV yinjira mu ngirabuzimafatizo no mu mara epithelial selile ikoresheje hPepT1. Ibi byerekana ko PepT1, nkabatwara, yorohereza KPV kwinjira muri selile kugirango ikore ingaruka zayo zo kurwanya inflammatory. Iyo imikorere ya PepT1 ihagaritswe, ingano ya KPV yinjira mu ngirabuzimafatizo iragabanuka, kandi ingaruka zayo zo kurwanya inflammatory nazo ziracika intege. Muri selile selile hamwe no gukomanga kumagambo ya PepT1, niyo yatanzwe mugihe kimwe, KPV yerekana kugabanya ingaruka mbi zo guhagarika ibikorwa bya NF-κB no kugabanya ururenda rwa cytokine itera inflammatory ugereranije na selile zifite imvugo isanzwe ya PepT1, bikomeza kwemeza uruhare rukomeye rwo guhuza PepT1 muburyo bwo kurwanya inflammatory KPV.
3. Kugena cytokine ikongora
Kubuza cytokine pro-inflammatory: KPV irashobora kubuza cyane umusaruro no kurekura cytokine nyinshi. TNF-α ni cytokine yingenzi mubisubizo byokongoka, ishoboye gukora selile yumubiri, itera kubyara izindi cytokine zitera inflammatory, no kwangiza ingirangingo. Muburyo butandukanye bwo gutwika, urwego rwimvugo ya TNF-α rwaragabanutse cyane nyuma yo kuvura KPV. Kurugero, muburyo bwa sodium sulfate iterwa nimbeba ya colitis yimbeba, kuvura hamwe na KPV byatumye igabanuka ryinshi rya mRNA ryerekana TNF-α mumyanya ndangagitsina, nkuko byagaragajwe nigihe nyacyo RT-PCR, ndetse no kugabanuka gukabije kwa poroteyine za TNF-α muri serumu, nkuko byagaragajwe na ELISA. IL-1β, IL-6, hamwe na cytokine itera inflammatory nayo yabujijwe na KPV. IL-1β irashobora gukurura cascade yaka umuriro, igateza imbere kurekura abandi bahuza. KPV irashobora kugabanya imvugo yayo no gusohora kwayo mumyanya yumuriro, bityo bikagabanya ubukana bwigisubizo.
Gutezimbere cytokine irwanya inflammatory: Usibye kubuza cytokine pro-inflammatory, KPV irashobora kandi guteza imbere imvugo ya cytokine irwanya inflammatory. Interleukin-10 (IL-10) ni cytokine ikomeye yo kurwanya inflammatory ishobora kubuza gukora ingirabuzimafatizo no kugabanya umusaruro wa cytokine itera umuriro.
4. Kugena ingirabuzimafatizo
Kugena imikorere ya T selile: T selile igira uruhare runini mugukingira indwara no kugenzura umuriro. Mugihe cyo gutwika, T selile ikora kandi ikarekura cytokine pro-inflammatory. Ubushakashatsi bwerekanye ko KPV ishobora kugenzura imikorere ya T selile. Mu bushakashatsi bwakozwe n'umurongo T w'umuntu T Jurkat, igihe selile ya Jurkat yashishikarizwaga na cytokine itera inflammatory, kongeramo KPV byabujije gukora selile T kandi bigabanya ururenda rwa cytokine itera inflammatory nka IFN-γ. Ibi birashobora kugerwaho muguhagarika NF-κB na MAPK byerekana inzira muri selile T. Byongeye kandi, mubyitegererezo bimwe byinyamanswa, nka CD45RB (hi) yerekana uburyo bwo gutwika imitsi, kuvura KPV birashobora kugenga kwinjiza T selile no gukora mumara, bikagabanya uduce duto twa T t selile nka Th1 na Th17, kandi bikongera umubare wuturemangingo T tugenga, bityo bikagabanya uburibwe bwo munda.
Guhindura imikorere ya macrophage: Macrophage ningirabuzimafatizo zikomeye zumudugudu mugisubizo cyokongoka kandi irashobora gushyirwa mubice bya M1 bikoreshwa muburyo busanzwe hamwe na macrophage ya M2 ikoreshwa ukurikije uko ikora. M1 macrophage isohora cytokine nyinshi zitera inflammatory, mugihe M2 macrophage ifite ibikorwa byo kurwanya inflammatory na tissue. KPV irashobora kugenga macrophage polarisation. Mu bushakashatsi bwa vitro bwerekanye ko igihe macrophage yashishikarizwaga na lipopolysaccharide (LPS) kugirango ihindurwe yerekeza ku bwoko bwa M1, ubufatanye bwa KPV bwabujije polarike ya macrophage yerekeza ku bwoko bwa M1, bigabanya imvugo ya M1 ya macrophage, mu gihe byateje imbere polarisiyasi yerekeza ku bwoko bwa M2 (nka Argin-1). Muri vivo inflammatory moderi, nka DSS iterwa na colitis yimbeba, kuvura hamwe na KPV byaviriyemo macrophage nyinshi mumyanya ndangagitsina ya polarike yerekeza mubwoko bwa M2, bityo bigabanya ibisubizo byumuriro no guteza imbere gusana ingirangingo.
5. Ingaruka zo gukingira ingirabuzimafatizo zo mu nda
Gutezimbere inzitizi ya epiteliyale: Inzitizi yumubiri ikorwa ningirabuzimafatizo zo mu nda ikora nk'umurongo wa mbere wo kwirinda indwara ziterwa na virusi. Mugihe cyo gutwika, imikorere mibi ya epithelial barrière iganisha kumikorere ya bagiteri no guhinduranya endotoxine, bikarushaho gukaza umurego. KPV irashobora kuzamura inzitizi yimikorere ya selile epithelial selile. Mu bushakashatsi bwakozwe na vitro selile, aho imirongo yo mu nda ya epiteliyale yo mu mara yavuwe hamwe na cytokine itera umuriro kugira ngo bigereranye ibidukikije, byatumye habaho kugabanuka kwa poroteyine zifatika (nka ZO-1 na occludin) kandi bikabangamira imikorere ya bariyeri. Nyamara, kwiyongera kwa KPV bikomeza kwerekana poroteyine zifatika zifatika, byongera imiyoboro ihuza imitsi, kandi bigarura imikorere yinzitizi yimitsi yo mu nda. Imbeba ya DSS iterwa na colitis ivurwa hamwe na KPV, immunohistochemie na analyse ya blot yo mu burengerazuba bwerekanye ko kwiyongera kwa poroteyine zifatika zifatika mu ngingo zifata imyanya ndangagitsina kandi bikagabanya ubwinjira mu mara, byerekana ko KPV irinda inzitizi zo mu nda muri vivo, igabanya ibitero by’ibintu byangiza, kandi igabanya ibisubizo by’umuriro.
Guteza imbere ikwirakwizwa ry'uturemangingo twa epiteliyale no gusana: Gutwika bishobora gutera kwangirika no gupfa kw'uturemangingo two mu mara, bikabangamira imikorere isanzwe y'amara. KPV ifite ubushobozi bwo guteza imbere ikwirakwizwa no gusana ingirabuzimafatizo zo mu nda. Mu bushakashatsi bw’umuco wa vitro bwerekanye ko kuvura ingirabuzimafatizo zo mu nda zangiritse hamwe na KPV byongereye ubwiyongere bw'utugingo ngengabuzima, nk'uko byagaragajwe na Kit Counting Cell (CCK-8). Byongeye kandi, isesengura rya immunofluorescence ryagaragaje imvugo yiyongera ya antigen nucleaire selile (PCNA), byerekana ko selile zari zimeze neza. Mu mbeba ya TNBS iterwa na ulcerative colitis imbeba, nyuma yo kuvurwa na hydrogel ya KPV / SH-PGA, ubushakashatsi bwakozwe mu mateka bwerekanye ko ibyangiritse ku ngirabuzimafatizo ya epiteliyale byakosowe, kandi ibikoresho byo mu bwoko bwa crypt byagarutse buhoro buhoro. Ibi birashobora kuba bifitanye isano no guteza imbere KPV yo gukwirakwiza epithelia selile no gusana, bifasha kugabanya uburibwe no guteza imbere ingirangingo zo munda.
Igishushanyo 2 KPV nubuvuzi muri DSS colitis.
6. Ingaruka za Antioxydeant
Kugena ibimenyetso bifitanye isano na okiside itera: Gutwika akenshi biherekejwe no guhagarika umutima kwa okiside, hamwe no kongera umusaruro wubwoko bwa ogisijeni (ROS) nubwoko bwa azote butera (RNS), bigatuma okiside yangiza ingirabuzimafatizo. KPV yerekana ingaruka za antioxydeant kandi irashobora kugenga ibimenyetso bya oxydeide. Muri moderi zimwe na zimwe zitwika, nka pamba ya granuloma yimipira yipamba hamwe nintanga yera yatewe nimbeba dorsal air sac synovitis, urugero rwinshi rwa malondialdehyde (MDA) no kugabanya ibikorwa bya superoxide (SOD) byagaragaye mumyanya yumubiri. Nyuma yo kuvura KPV, urwego rwa MDA rwaragabanutse cyane, kandi ibikorwa bya SOD byariyongereye. MDA ni umusaruro wa lipide peroxidation, kandi kugabanuka kwayo byerekana kugabanuka kwa lipide peroxidation yangiza selile; SOD ni enzyme yingenzi ya antioxydeant, kandi ibikorwa byayo byiyongera byerekana ubushobozi bwongerewe imbaraga zo gushakisha radicals yubusa. KPV irashobora kugabanya kwangirika kwa okiside mumyanya yumubiri muguhindura urugero rwa oxydeide, bityo bikagira ingaruka zo kurwanya inflammatory.
7. Ubundi buryo bushoboka
Isano na reseptor ya melanocortin: KPV ni tripeptide ikomoka kuri α-MSH. Nubwo ingaruka zayo zo kurwanya inflammatory zitigenga igice cya MC1R cyerekana, zishobora kuba zifitanye isano na MC1R mubice bimwe. Mu nyamaswa zigaragaza MC1Re / e, ubuvuzi bwa KPV nyuma ya colitis iterwa na DSS buracyafite ingaruka zikomeye zo kurwanya inflammatory, bukiza inyamaswa zose zo mu itsinda ry’abaganga mu rupfu mu gihe cya kolite iterwa na DSS, byerekana ko ingaruka za KPV zirwanya indwara byibuze zidafite aho zihuriye n’ibimenyetso bya MC1R. Mu nyamaswa zifite imvugo isanzwe ya MC1R, KPV irashobora kongera ingaruka zo kurwanya inflammatory mugukorana na MC1R cyangwa kugenzura inzira zayo zerekana inzira.
Ingaruka zo kurwanya inflammatory ya KPV
1. Uruhare muburyo bwo gutwika amara
Moderi ya DSS iterwa na colitis: Muburyo bwa DSS iterwa nimbeba ya colitis, KPV yerekanye ingaruka zikomeye zo kurwanya inflammatory. Kubijyanye no guhindura ibiro, imbeba zavuwe na KPV zagaruye ibiro byazo mbere kandi cyane ugereranije nimbeba zitavuwe. Ubushakashatsi bwakozwe ku mateka bwerekanye ko igabanuka ry’imyororokere mu mitsi y’imbeba zavuwe na KPV, bishimangirwa no kugabanuka gukabije kwa myeloperoxidase (MPO). MPO ni enzyme iboneka muri neutrophile, kandi urwego rwibikorwa byayo rugaragaza urugero rwimikorere ya selile yinjira mubice. Kugabanuka kwibikorwa bya MPO nyuma yubuvuzi bwa KPV byerekana kugabanuka kwa neutrophil kwinjira mumyanya ndangagitsina no kugabanya ibisubizo byumuriro. Mu gutahura imvugo ya mRNA ya cytokine itera inflammatory mu mitsi ya colonike, nka TNF-α na IL-1β, byagaragaye ko kuvura KPV byagabanije cyane imvugo ya cytokine itera umuriro. KPV yagabanije ibimenyetso bya kolite iterwa na DSS iturutse mu bintu byinshi, harimo kugabanya ubwiyongere bw'uturemangingo twa selile, kugabanya imvugo yibintu, no guteza imbere ibiro.
CD45RB (hi) icyitegererezo cyo gutwika: Muri moderi ya CD45RB (hi) yerekana umuriro, KPV nayo yerekanye ingaruka nziza zo kurwanya inflammatory. Iyi moderi yatewe no kwimura selile T zigaragaza cyane CD45RB mu mbeba zidafite ubudahangarwa. Nyuma yo kuvura KPV, imbeba zagaragaje ibimenyetso byerekana umuriro, gukira buhoro buhoro, hamwe n’isuzuma ry’amateka ryagaragaje impinduka zo mu nda zagabanutse. Itsinda ryavuwe na KPV ryerekanye ko igabanuka ryimyanya ndangagitsina kandi ryagabanutse kwangirika kwimiterere yinyama zo munda, byerekana ko KPV igabanya CD45RB (hi) -yatewe no gutwika amara kandi igasubiza imiterere yimikorere yimitsi yo mumara.
Ubwoko bwa TNBS buterwa na ulcerative colitis moderi: Muri TNBS iterwa na ulcerative colitis imbeba, KPV nayo yerekanye ingaruka zikomeye zo kuvura. Nyuma yo gutanga hydrogel ya KPV / SH-PGA neza ku mbeba, ibimenyetso bya colitis byateye imbere ku buryo bugaragara. Urwego rwo kugabanya ibiro mu mbeba rwaragabanutse, kandi amanota y'ibikorwa by'indwara (DAI) yagabanutse. Amanota ya DAI yerekana neza ibipimo nkimpinduka zuburemere bwimibiri yimbeba, ibiranga fecal, na hematochesia. Kugabanuka kwayo byerekana ko hydrogel ya KPV / SH-PGA ishobora kugabanya neza ubukana bwa TNBS iterwa na kolite yanduye. Kuvura hydrogel ya KPV / SH-PGA birinda kandi kugabanuka kw'imbeba mu mbeba, kugabanya urugero rwa myeloperoxidase ya colonike, no kugarura imiterere ya morfologiya ya colonike, harimo inzitizi ya epiteliyale, kode, hamwe na selile zuzuye. Imvugo ya cytokine itera inflammatory, TNF-α na IL-6, mumyanya ndangagitsina nayo yagabanutse ku buryo bugaragara, bikomeza kwerekana ingaruka zo kurwanya inflammatory ya KPV muburyo bwa TNBS buterwa na ulcerite colitis.
Umwanzuro
KPV, nka tripeptide ifite imiti igabanya ubukana, yerekana ingaruka zitanga ikizere mukurinda no kuvura indwara zo munda nizindi ndwara zitandukanye ziterwa no gutwika. Uburyo bwayo bwo kurwanya inflammatory bukubiyemo ibintu byinshi, harimo kugenzura inzira zerekana ibimenyetso bya selile, guhagarika umutima, no guhindura apoptose na autophagy.
Inkomoko
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Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
