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1kits （10Ibikoresho）
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Ucture Imiterere ya TKPV
Inkomoko ： PubChem |
IUPAC Yegeranye ： H-Lys-Pro-Val-OH Inzira ya molekulari: C 16H 30N 4O.4 Uburemere bwa molekuline: 342.43g / mol Numero ya CAS: 67727-97-3 PubChem CID: 125672 Synonyme: Msh (11-13) ； alpha-Msh (11-13) ； IGIKORWA- (11-13) |
Research Ubushakashatsi bwa KPV
Ni ubuhe bushakashatsi bwakozwe na KPV?
KPV ni tripeptide ikomoka kuri hormone itera α-melanocyte (α-MSH). α-MSH ni imisemburo ya polypeptide ifite imikorere myinshi yibinyabuzima, igira uruhare runini muguhindura ibara ryuruhu, kugenzura ubudahangarwa, nibindi bintu. Nkigice cya α-MSH, KPV yitaruye kandi yizwe cyane. Nubwo hari intambwe imaze guterwa mu rwego rwubuvuzi mu myaka yashize, uburyo bwo kuvura indwara zifata amara (IBD) buracyashimishije, kandi umubare wo kubaga ukomeje kuba mwinshi. Kubwibyo, gushakisha uburyo bushya kandi bunoze bwo kuvura bwabaye umurimo wihutirwa. IBD ikubiyemo colitis ibisebe, indwara ya Crohn, nibindi, birangwa no gutwika amara karande kandi bigira ingaruka zikomeye kumibereho yabarwayi. Uburyo bwo kuvura burimo kuvura imiti no kuvura kubaga, ariko byombi bifite aho bigarukira. Mu myaka yashize, ingaruka zo kurwanya peptide ya melanocortine nka α-MSH zasobanuwe muri colitis dextran sulfate sodium (DSS) mu mbeba. Ibi biratanga ibimenyetso byo kwiga ubushobozi bwo kurwanya inflammatory ya KPV. α-MSH ifite imirimo nko kugenzura ubudahangarwa no kugabanya ibicanwa, kandi tripeptide KPV ikomokaho nayo ifatwa nkaho ishobora kuba ifite imiti igabanya ubukana.
Nubuhe buryo bwo gukora bwa KPV?
Uburyo bwibikorwa muri kolite y ibisebe
Kunoza ituze hamwe nubuyobozi bukosora:
KPV (Lys-Pro-Val) ni tripeptide ikomoka kuri α-MSH (imisemburo itera α-melanocyte) kandi ifite ingaruka zo kurwanya kolite. Nyamara, igisubizo cya KPV ntigihungabana cyane mugihe cyo kuyobora urukiramende, bigira ingaruka kubikorwa byo kuvura. Mu bushakashatsi bwakozwe, cysteamine yashizwemo acid-polyglutamic aside (SH-PGA) yashizwemo no guhuza sisitemu hamwe nitsinda rya carboxyl ya γ-PGA. Utarinze gukoresha umukozi uhuza, 4% ya polymer ya SH-PGA hydrogel yashizweho binyuze mukwiyambukiranya-guhuza amatsinda ya sulfhydryl. Hydrogel ya KPV / SH-PGA yerekanaga modulus ya elastike (G ') irenze modulus ihuye na viscous (G' ') kuri 0.01-10 Hz, ikagaragaza uburyo bwiza bwo gukanika no gukata imisatsi, bifasha ubuyobozi bwurukiramende. Muri icyo gihe, umutekano wa KPV muri hydrogel ya SH-PGA wariyongereye cyane. 30% gusa ya KPV yarekuwe muri hydrogel ya KPV / SH-PGA muminota 20, ikurikirwa nimyitwarire ikomeza yo kurekura [1].
Kugabanya ibimenyetso bya kolite:
Binyuze mu bushakashatsi bwakozwe ku mbeba zifite colitis ulcerative yatewe na acide 2,4,6-trinitrobenzene sulfonique (TNBS), byemejwe ko uburyo bwo kuvura hydrogel ya KPV / SH-PGA kuri colitis bwemejwe. Nyuma yubuyobozi bugororotse bwa hydrogel ya KPV / SH-PGA, ibimenyetso bya colitis harimo kugabanya ibiro hamwe n amanota yibikorwa byindwara byagabanutse cyane. Byongeye kandi, kuvura hamwe na hydrogel ya KPV / SH-PGA byabujije kugabanuka kwa colon mu mbeba zatewe na TNBS kandi bigabanya urwego rwa myeloperoxidase ya colonike. Nyuma yo kuvurwa na hydrogel ya KPV / SH-PGA, morphologie yumura, harimo inzitizi ya epiteliyale, kode, hamwe na selile ya goblet idasubirwaho. Muri icyo gihe, hydrogel ya KPV / SH-PGA yagabanije imvugo ya cytokine itera umuriro nka feri yibibyimba α na interleukin 6 [1].
Uburyo bwibikorwa muburyo bwimbeba yindwara yumura
Ubwoko bwa DSS colitis: Muburyo bwa DSS colitis, kuvura hamwe na KPV byatumye gukira hakiri kare kandi byongera cyane kugarura ibiro. Dukurikije amateka, kwinjira mu mbeba zavuwe na KPV byagabanutse ku buryo bugaragara, ibyo bikaba byemejwe no kugabanuka gukabije kw'ibikorwa bya myeloperoxidase (MPO) mu nyama zo mu nda nyuma yo kuvura KPV [2].
CD45RB (hi) kwimura colitis moderi:
Gushyigikira ibyavuzwe haruguru, kuvura KPV ya colitis yimuwe byatumye gukira indwara, gukira ibiro, no kugabanuka kwimpinduka ziterwa no kumenya amateka [2].
MC1Re / e icyitegererezo cyimbeba:
Imbeba zerekana reseptor ya melanocortin-1 idakora (MC1Re / e), ubuvuzi bwa KPV bwarokoye inyamaswa zose zo mu itsinda ryivura urupfu mu gihe cya DSS colitis. Ibi byerekana ko ingaruka zo kurwanya inflammatory ya KPV zisa nkaho zitigenga byibuze igice cya MC1R cyerekana [2].
Uburyo bwibikorwa muri bronchial epithelial selile inflammation
Ndabuza ibimenyetso bya NF-κB:
Mu ngirabuzimafatizo z'umuntu zidapfa, peptide KPV na melanocortine ifitanye isano na peptide KPV na agonist α-MSH ya epitelium yo mu kirere (MC3R) yabujije ibimenyetso bya NF-κB mu kubuza kwinjiza kirimbuzi p65RelA no gukora epiteliyale MC3R. By'umwihariko, ingaruka za KPV zijyanye no gutumiza mu kirere kwa kirimbuzi, zishobora kubuza guhinduranya kirimbuzi p65RelA yanditseho YFP. Muri icyo gihe, imbuga zihuza KPV na Imp-α / β ziri kuri p65RelA, birashoboka ko harimo guhagarika importin-α armadillo domaine 7 na 8 [3].
Uburyo bwibikorwa muri chimiotherapie iterwa na mucosite yo mu kanwa
Antibacterial, anti-inflammatory, hamwe ningaruka zo gusana:
Gukoresha ubushyuhe bukabije bwa PLGA-PEG-PLGA (PPP) nka matrix na epigallocatechin-3-gallate (EGCG) hamwe na antibacterial yibikorwa nkibikoresho byongerera imbaraga, hydrogel (PPP_E) byateguwe neza. Tripeptide KPV yasheshwe mubisubizo bikonje PPP_2% E ibanziriza nkumuti wintangarugero wo gutegura hydrogel ya KPV @ PPP_2% E. Igikorwa cyo kurwanya inflammatory nubushobozi bwo guteza imbere kwimuka kwa selile ya KPV muri hydrogel ya PPP-2% E byakomeje neza. Mubyongeyeho, KPV @ PPP_2% E yagize ingaruka zikomeye za antibacterial kurwanya Staphylococcus aureus. Iyo hydrogel ya KPV @ PPP_2% E yakoreshejwe kuri mucosa ya gingival yimbeba hamwe na chimiotherapie iterwa na mucosite yo mu kanwa, irashobora guhinduka vuba muri hydrogel kandi igafatira ku gikomere amasaha 7, igahindura cyane ibiryo ndetse no kugarura imbeba. Muri icyo gihe, mugutezimbere imvugo ya CK10 na PCNA, hydrogel ya KPV @ PPP_E nayo yasannye neza morphologie ya tissue ya gingiva yakomeretse. Byongeye kandi, hydrogel ya KPV @ PPP_2% E yabujije cyane cytokine ikongora harimo IL-1β na TNF-α, kandi icyarimwe igenga IL-10 [4].
Inkomoko: PubMed [5]
Ni ubuhe buryo bwo kuvura imiti ya KPV?
Umuti wa colitis
Ubuyobozi binyuze mu guhuza hydrogel:
Mu bushakashatsi bwakozwe, cysteamine yashizwemo aside-polyglutamic aside (SH-PGA) yashizwemo hanyuma ikorwa muri hydrogel kugirango ihagarike tripeptide KPV [1] . Hydrogel ya KPV / SH-PGA yerekanye ingaruka nziza zo kuvura muburyo bwimbeba ya colitis ibisebe byatewe na aside 2,4,6-trinitrobenzene sulfonique (TNBS). By'umwihariko, nyuma yubuyobozi bwurukiramende, ibimenyetso bya colitis nko kugabanya ibiro hamwe n amanota yibikorwa byibikorwa byindwara byagabanutse cyane, kandi birashobora no gukumira kugabanuka kwimitsi yimbeba zatewe na TNBS kandi bikagabanya urwego rwa myeloperoxidase ya colonike. Muri icyo gihe, morphologie ya colon, harimo inzitizi ya epiteliyale, crypts, hamwe na selile ya goblet idasubirwaho, yagaruwe nyuma yo kuvurwa na hydrogel ya KPV / SH-PGA, kandi hydrogel nayo yagabanije imvugo ya cytokine itera umuriro nka feri ya niyose ya α na interleukin 6.
Ubuyobozi binyuze mumiyoboro ibiri ya hydrogel:
Ubundi bushakashatsi bwubatsemo hydrogel ebyiri (PMSP) yakozwe na acide γ-polyglutamic acide na acide γ-polyglutamic acide binyuze muri thiol-maleimide ihuza no kwikuramo okisiyumu [5] . Iyi hydrogel irashobora gukurikiza byumwihariko mucosa yaka kuruta mucosa nzima, kandi ifite imbaraga zumukanishi hamwe na biologiya. KPV, nk'umuti w'icyitegererezo, ifatwa byoroshye na PMSP binyuze mu mikoranire ya electrostatike, bityo igakomeza ibikorwa by’ibinyabuzima igihe kirekire mu gihe cy'ubushyuhe bwinshi. Imbeba zifite colitis zatewe na TNBS, nyuma yubuyobozi bukuru bwa PMSP-KPV, ingaruka zo kugabanya KPV kuri colitis zateye imbere cyane, kandi inzitizi ya epiteliyale yinkondo yagaruwe neza. Byongeye kandi, PMSP-KPV yanagengaga ibimera byo mu mara kandi byongera cyane ubwinshi bwa mikorobe ngirakamaro mu mara.
Kuri chimiotherapie iterwa na mucosite yo mu kanwa
Hateguwe hydrogel (PPP_E) mu mwanya wa mucosal wifashishije ubushyuhe bwa PLGA-PEG-PLGA (PPP) nka matrix na epigallocatechin-3-gallate (EGCG) nk'iyongerera imbaraga [4] . Tripeptide KPV yasheshwe mubisubizo bikonje PPP_2% E ibanziriza nkumuti wintangarugero wo gutegura hydrogel ya KPV @ PPP_2% E. Iyi hydrogel ifite anti-inflammatory, antibacterial, no gusana ingaruka kuri chimiotherapie iterwa na mucosite yo mu kanwa. By'umwihariko, irashobora gukomeza ibikorwa byo kurwanya inflammatory ya KPV hamwe nubushobozi bwo guteza imbere kwimuka kwakagari, kandi ikagira ingaruka zikomeye za antibacterial kurwanya Staphylococcus aureus. Nyuma yubuyobozi kuri mucosa ya gingival yimbeba hamwe na chimiotherapie iterwa na mucosite yo mu kanwa, igisubizo cya PPP_2% E cyahise gihinduka hydrogel kandi gifata hejuru y igikomere amasaha 7. Kuvura hamwe na KPV @ PPP_2% E hydrogel byateje imbere cyane ibiryo no kugarura ibiro byimbeba, biteza imbere imvugo ya CK10 na PCNA, bisana neza morphologie yimitsi ya gingiva yakomeretse, kandi icyarimwe byabujije cyane cytokine ikongora nka IL-1β na TNF-α, kandi ihindura imvugo ya IL-10. Iyi hydrogel kandi igira ingaruka za antibacterial ku bikomere bya gingival yanduye yanduye methicilline irwanya Staphylococcus aureus (MRSA), kandi ikabuza cyane kwinjira mu ngirabuzimafatizo zinjira mu ngingo za subucosal.
Kuvura indwara zifata umura
Ubushakashatsi bumwe bwerekanye ko KPV ishobora kuba imiti mishya yo kuvura indwara zifata amara (IBD) [6] . Mu mara yo mu mara ya epithelia yumuntu (Caco2-BBE na HT29-Cl.19A) hamwe na selile T yumuntu (Jurkat), nyuma yo gukangurwa na cytokine itera inflammatory, kongeramo KPV birashobora kubuza gukora inzira ya NF-κB na MAP kinase yerekana inzira kandi bikagabanya gusohora kwa cytokine. Ubushakashatsi bwerekanye ko KPV ikora binyuze muri hPepT1 igaragara mu ngirabuzimafatizo no mu mara. Byongeye kandi, muburyo bwimbeba ya colitis iterwa na dextran sulfate sodium (DSS) na TNBS, ubuyobozi bwo mu kanwa bwa KPV bushobora kugabanya imvugo ya cytokine itera umuriro hamwe na kolite.
Mu gusoza, nkibintu bioaktike bifite imbaraga nyinshi, KPV yerekana ibyiza byihariye mukuvura indwara zitandukanye. Mu rwego rwindwara zifata amara, haba mubushakashatsi bwikitegererezo cyimbeba cyangwa mubushakashatsi bwuburyo butandukanye bwubuyobozi bwa colitis ibisebe, KPV irashobora kugabanya neza kwinjira kwifata, kunoza imiterere yimitsi, kugenga imvugo ya cytokine, no kugira ingaruka zikomeye zo kurwanya inflammatory hakoreshejwe uburyo bwo gutwara PepT1. Mu kuvura indwara ya chimiotherapie iterwa na mucosite yo mu kanwa, hydrogel irimo KPV yateguwe hamwe na matrix yihariye kandi yongerera imbaraga adhesion ntishobora gukomeza ibikorwa byayo byo kurwanya no kwimuka kwimuka gusa ahubwo ifite n'ubushobozi bukomeye bwa antibacterial, kunoza cyane ibimenyetso bifitanye isano nimbeba no guteza imbere gusana ingirangingo. Nubwo ubu amavuriro akoreshwa muri KPV aracyari make, ibisubizo byubushakashatsi bihari byerekana neza agaciro kayo ko kuvura. Mu bihe biri imbere, niba hari intambwe ishobora kugerwaho mu bushakashatsi bwimbitse ku bijyanye no guteza imbere ibiyobyabwenge no gutanga umusaruro, kwagura ibimenyetso by’amavuriro, no gushimangira gukurikirana no gucunga amavuriro, biteganijwe ko KPV izazana uburyo bwiza bwo kuvura bwiza kandi bunoze ku barwayi benshi kandi bukagira uruhare runini mu kuvura amavuriro.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Dalmasso G ni umushakashatsi mubijyanye nubuvuzi, hamwe nubuyobozi bwubushakashatsi bukubiyemo ubuvuzi, ibinyabuzima, na genetika, mubindi bice. Yakoze mu bigo byinshi bizwi, birimo Universite Clermont Auvergne (UCA), CHU Clermont Ferrand, INRAE, Institut National de la Sante et de la Recherche Medicale (Inserm), Clermont Univ, kaminuza ya Jeworujiya, kaminuza ya Emory, Universite Cote d'Azur, na Universidad Nacional Rio Cuarto. Izi nzego zizwi cyane mu nzego zazo, kandi ubufatanye bwa Dalmasso G na bo bwagize uruhare mu guteza imbere amasomo ajyanye nayo. Ibyavuye mu bushakashatsi bwe bishobora kuba bifite akamaro kanini mu guteza imbere ubumenyi bw’ubuvuzi, cyane cyane mu kuzamura umusaruro w’ubuvuzi n’ubuzima bw’abarwayi. Dalmasso G yanditse murutonde rwibisobanuro [6].
