By Cocer Peptides 
1 ọnwa gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Ozi bụ isi gbasara KPV
KPV bụ tripeptide nwere nnukwu ihe mgbochi mkpali, nke na-enyere ya aka ịrụ ọrụ n'ọtụtụ mpaghara.
Ọnụọgụ 1 Mmetụta ọgwụgwọ nke HA-KPV-NPs megide UC Oral management nke HA-KPV-NPs agbakwunyere na hydrogel (chitosan / alginate) na-enye mmetụta ọgwụgwọ jikọtara ọnụ megide UC site n'ịkwalite ọgwụgwọ mucosa na ibelata mbufụt.
Usoro mgbochi mkpali nke KPV
1. Iwu nke ụzọ nrịbama cell
Ụzọ nrịbama NF-κB: NF-κB bụ isi ihe ntụgharị ederede na-arụ ọrụ etiti na nzaghachi mkpali. Mgbe mkpụrụ ndụ na-ekpughere ihe mkpali na-egbuke egbuke, NF-κB na-atụgharị site na cytoplasm gaa na nucleus, na-amalite nsụgharị nke mkpụrụ ndụ cytokine pro-inflammatory. KPV nwere ike igbochi ọrụ NF-κB. N'ime mkpụrụ ndụ epithelial intestinal mmadụ na mkpụrụ ndụ T mmadụ, a na-akpali mkpụrụ ndụ na cytokines pro-inflammatory, na KPV gbakwunyere n'otu oge. N'iji usoro ndị dị ka NF-κB luciferase gene reporter assays, protein immunoblotting, real-time reverse transcription polymerase chain reaction, na enzyme-linked immunosorbent assay (ELISA), a chọpụtara na KPV na nchịkọta nanomolar nwere ike igbochi ọrụ NF-κB, si otú ahụ na-ebelata ihe nzuzo nke cytokines pro-inflammatory. Usoro a dị oke mkpa na nhazi nke mbufụt nke eriri afọ, dị ka oke ọrụ nke NF-κB na sel epithelial intestinal na mkpụrụ ndụ na-alụso ọrịa ọgụ bụ akụkụ dị mkpa nke ọrịa obi na-egbuke egbuke (IBD) na ọnọdụ mkpali nke eriri afọ ndị ọzọ.
Ụzọ nrịbama nke MAP kinase: Ụzọ nrịbama nke mitogen-activated protein kinase (MAPK) bụ ụzọ ọzọ dị mkpa nhazi usoro na nzaghachi mkpali, gụnyere extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), na p38 MAPK. A na-eme ka kinases ndị a na-arụ ọrụ mgbe mkpụrụ ndụ na-ekpughe ihe mkpali na-akpali akpali, na-eduga na phosphorylation nke ihe odide ederede na-akwalite okwu nke mkpụrụ ndụ ihe nketa metụtara mbufụt. KPV nwekwara ike igbochi ụzọ mgbama MAP kinase. Mgbe a na-ekpughere mkpụrụ ndụ na mkpali mkpali, KPV nwere ike igbochi ọrụ MAPK, na-ebelata phosphorylation ya nke ihe odide ederede, si otú ahụ na-ebelata mmepụta nke cytokines pro-inflammatory. Na ọnọdụ mkpali, ịgbalite p38 MAPK na-eduga n'ịbawanye nkwupụta nke cytokines pro-inflammatory dị ka TNF-a na IL-6, ebe KPV nwere ike igbochi ọrụ p38 MAPK, na-ebelata ihe nzuzo nke cytokines ndị a ma si otú a na-ebelata nzaghachi mkpali.
2. Mmetụta mgbasa ozi na-ebugharị cell
Onye na-ebufe PepT1: PepT1 bụ onye na-ebufe di/tripeptide na-egosipụtakarị na eriri afọ mana ọ na-ebute ya na colon n'oge IBD. Mmetụta mgbochi mkpali nke KPV bụ nke PepT1 na-edozi akụkụ ụfọdụ. N'ime nnwale nnabata, a na-eji KPV oyi dị ka onye na-egbochi asọmpi maka hPepT1 dị ka mkpụrụ okwu redioactive akpọrọ, ma ọ bụ [⊃3; H] KPV ka ejiri chọpụta njirimara kinetic nke nnabata KPV. KPV na-abanye n'ime sel na-alụso ọrịa ọgụ na sel epithelial intestinal site na hPepT1. Nke a na-egosi na PepT1, dị ka onye na-ebufe, na-eme ka KPV banye n'ime sel iji mepụta mmetụta mgbochi mkpali ya. Mgbe a na-egbochi ọrụ PepT1, ọnụọgụ nke KPV na-abanye n'ime sel na-ebelata, na mmetụta mgbochi mkpali ya na-adalata nke ọma. N'ime ụdị sel nwere knockdown nke okwu PepT1, ọbụlagodi mgbe a na-enye ya n'otu ntinye uche, KPV na-egosipụta nke ọma belata mmetụta mgbochi na ntinye NF-κB na mbelata nzuzo nke cytokines pro-inflammatory ma e jiri ya tụnyere sel nwere okwu PepT1 nkịtị, na-akwado ọrụ mgbasa ozi dị mkpa nke PepT1 na usoro mgbochi mkpali nke KPV.
3. Iwu nke cytokines na-egbuke egbuke
Mgbochi nke cytokines pro-inflammatory: KPV nwere ike igbochi mmepụta na ntọhapụ nke ọtụtụ cytokines pro-inflammatory. TNF-α bụ cytokine bụ isi na nzaghachi mkpali, nke nwere ike ime ka mkpụrụ ndụ na-alụso ọrịa ọgụ rụọ ọrụ, na-ebute mmepụta nke cytokines pro-inflammatory ndị ọzọ, na-akpata mmebi anụ ahụ. N'ụdị ụdị mkpali dị iche iche, ọkwa nkwupụta nke TNF-a belatara nke ukwuu mgbe ọgwụgwọ KPV gasịrị. Dịka ọmụmaatụ, na ụdị mouse colitis nke sodium sulfate na-ebute, ọgwụgwọ na KPV mere ka mbelata dị ukwuu na nkwupụta mRNA nke TNF-α na anụ ahụ, dị ka achọpụtara site na RT-PCR n'ezie, na mbelata dị ukwuu na protein ọdịnaya nke TNF-α na serum, dị ka ELISA chọpụtara. IL-1β, IL-6, na cytokines ndị ọzọ pro-inflammatory bụkwa KPV gbochiri. IL-1β nwere ike ịkpalite mmeghachi omume cascade mkpali, na-akwalite ntọhapụ nke ndị ogbugbo mkpali ndị ọzọ. KPV nwere ike ibelata nkwupụta ya na nzuzo ya na anụ ahụ na-egbuke egbuke, si otú a na-ebelata ike nke nzaghachi mkpali.
Nkwalite nke cytokines mgbochi mkpali: Na mgbakwunye na igbochi cytokines pro-inflammatory, KPV nwekwara ike ịkwalite nkwupụta nke cytokines mgbochi mkpali. Interleukin-10 (IL-10) bụ cytokine dị mkpa na-egbochi mkpali nke nwere ike igbochi ọrụ nke mkpụrụ ndụ na-alụso ọrịa ọgụ ma belata mmepụta nke cytokines pro-inflammatory.
4. Iwu nke sel ndị na-alụso ọrịa ọgụ
Ịchịkwa ọrụ cell T: mkpụrụ ndụ T na-arụ ọrụ dị mkpa na nzaghachi mgbochi na nchịkwa mbufụt. N'okpuru ọnọdụ mkpali, mkpụrụ ndụ T na-arụ ọrụ ma zoo cytokines pro-inflammatory. Nnyocha egosiwo na KPV nwere ike ịhazi ọrụ cell T. Na nnwale nke mmadụ T cell line Jurkat, mgbe mkpụrụ ndụ Jurkat nwere cytokines pro-inflammatory, mgbakwunye nke KPV gbochiri ọrụ cell T ma belata nzuzo nke cytokines pro-inflammatory dị ka IFN-γ. Enwere ike nweta nke a site na igbochi NF-κB na ụzọ akara MAPK n'ime mkpụrụ ndụ T. Na mgbakwunye, n'ụdị anụmanụ ụfọdụ, dị ka CD45RB (hi) ụdị mbufụt nke colonic, ọgwụgwọ KPV nwere ike ịhazi ntinye nke cell T ma rụọ ọrụ n'ime eriri afọ, belata mbufụt nke mkpụrụ ndụ T cell dị ka sel Th1 na Th17, ma mee ka ọnụọgụ nke mkpụrụ ndụ T na-achịkwa, si otú ahụ na-ebelata mbufụt nke eriri afọ.
Mgbanwe nke ọrụ macrophage: Macrophages bụ mkpụrụ ndụ mgbochi dị mkpa na nzaghachi mkpali na enwere ike kewaa ya n'ime macrophages M1 na-arụ ọrụ nke ọma yana M2 macrophages na-arụ ọrụ ọzọ dabere na ọnọdụ mmalite ha. M1 macrophages na-ezobe nnukwu cytokines pro-inflammatory, ebe M2 macrophages nwere ọrụ mgbochi mkpali na ịrụzi anụ ahụ. KPV nwere ike ịhazi macrophage polarization. Nnwale in vitro gosiri na mgbe a na-akpali macrophages na lipopolysaccharide (LPS) iji mee ka ọ dị mma na ụdị M1, nchịkwa nke KPV na-egbochi macrophage polarization n'ebe ụdị M1, belata okwu nke M1 macrophage markers, ebe ha na-akwalite polarization ha n'ebe ụdị M2, na-amụba okwu nke M2 markers, na-amụba okwu nke M2. Arg-1). Na ụdị vivo mkpali, dị ka DSS na-ebute colitis na ụmụ oke, ọgwụgwọ na KPV mere ka ọtụtụ macrophages dị na eriri afọ na-eme ka ọ dị na ụdị M2, si otú ahụ na-ebelata nzaghachi mkpali na ịkwalite nrụzi anụ ahụ.
5. Mmetụta nchebe na sel epithelial intestinal
Ịkwalite ọrụ mgbochi epithelial: Ihe mgbochi anụ ahụ nke mkpụrụ ndụ epithelial intestinal hibere na-eje ozi dị ka ụzọ mbụ nke nchebe megide nje na mwakpo ihe na-emerụ ahụ. Na steeti mkpali, arụrụ arụ ọrụ mgbochi nke eriri afọ na-eduga na ntụgharị nje na nje endotoxin, na-abawanye nzaghachi mkpali. KPV nwere ike ịkwalite ọrụ mgbochi nke sel epithelial intestinal. Nnwale sel vitro, ebe ejiri cytokines pro-inflammatory na-emeso eriri afọ epithelial cytokines iji mee ka ọnọdụ mkpasu iwe, butere mbelata ngosipụta nke protein njikọ siri ike (dị ka ZO-1 na occludin) yana arụrụ ọrụ mgbochi. Otú ọ dị, mgbakwunye nke KPV na-ejigide okwu nke protein njikọ siri ike, na-eme ka njikọ intercellular dịkwuo elu, ma weghachite ọrụ mgbochi nke mkpụrụ ndụ epithelial intestinal. N'ime ụmụ oke colitis nke DSS na-emeso ya na KPV, immunohistochemistry na Western blot analysis kpughere mmụba nke protein njikọ siri ike na anụ ahụ na mbelata nke eriri afọ, na-egosi na KPV na-echebe ihe mgbochi eriri afọ nke eriri afọ na vivo, na-ebelata mbuso agha nke ihe na-emerụ ahụ, ma na-ebelata nzaghachi mkpali.
Na-akwalite mmụba cell epithelial na nrụzi: Mbufụt nwere ike ime ka mmebi na ọnwụ nke mkpụrụ ndụ epithelial intestinal, na-emebi ọrụ eriri afọ nkịtị. KPV nwere ikike ịkwalite mmụba na mmezi nke mkpụrụ ndụ epithelial intestinal. Nnwale omenala sel vitro gosiri na iji KPV agwọ mkpụrụ ndụ nke eriri afọ mebiri emebi na-abawanye ụba cell, dị ka a chọpụtara site na Kit Counting Kit (CCK-8). Na mgbakwunye, nyocha nke immunofluorescence kpughere nkwuputa mmụba nke cell nuklear antigen (PCNA), na-egosi na mkpụrụ ndụ nọ n'ọnọdụ ịgbasawanye ike. N'ime ụdị oke ọnya ulcerative colitis nke TNBS kpatara, mgbe a gwọchara ya na KPV/SH-PGA hydrogel, nchọpụta akụkọ ihe mere eme gosiri na a rụziri mmebi nke mkpụrụ ndụ epithelial colonic, na akụkụ crypt ji nwayọọ nwayọọ laghachi na nkịtị. Nke a nwere ike jikọta na nkwalite KPV maka mmụba na nrụzi nke cell epithelial, nke na-enyere aka belata mbufụt ma kwalite mgbake anụ ahụ eriri afọ.
Ọgụgụ 2 KPV bụ ọgwụgwọ na DSS colitis.
6. Mmetụta antioxidant
Iwu nke ihe nrịbama metụtara nrụgide oxidative: A na-esonyekarị ọkụ ọkụ na mmeghachi omume nrụgide oxidative, na-abawanye mmepụta nke ụdị oxygen na-emeghachi omume (ROS) na ụdị nitrogen na-emeghachi omume (RNS), na-eduga na mmebi oxidative na sel na anụ ahụ. KPV na-egosipụta mmetụta antioxidant ma nwee ike ịhazi akara ndị metụtara nrụgide oxidative. N'ụfọdụ ụdị mkpasu iwe, dị ka ụdị granuloma òké na-eme ka bọọlụ na akwa akwa na-acha ọcha na-ebute oke oke ikuku sac synovitis, ọkwa dị elu nke malondialdehyde (MDA) na mbelata ọrụ superoxide dismutase (SOD) ka achọpụtara na anụ ahụ na-akpasu iwe. Na-eso ọgwụgwọ KPV, ọkwa MDA belatara nke ukwuu, yana ọrụ SOD mụbara. MDA bụ ngwaahịa nke lipid peroxidation, na ọkwa ya belatara na-egosi mbelata peroxidation lipid mmebi nke mkpụrụ ndụ; SOD bụ enzyme antioxidant dị mkpa, yana mmụba ọrụ ya na-egosi ike nwelite ike ịbọ ọbọ free radicals. KPV nwere ike ibelata mmebi oxidative n'ime anụ ahụ na-egbuke egbuke site n'ịhazi ọkwa nrụgide oxidative, si otú ahụ na-enwe mmetụta mgbochi mkpali.
7. Usoro ndị ọzọ nwere ike ime
Mmekọrịta ya na melanocortin nnata: KPV bụ tripeptide sitere na α-MSH. Ọ bụ ezie na mmetụta mgbochi mkpali ya na-adabere na akụkụ nke nrịbama MC1R, enwere ike jikọta ha na MC1R n'ọnọdụ ụfọdụ. N'ime ụmụ anụmanụ na-egosipụta MC1Re / e, ọgwụgwọ KPV na-esochi DSS-induced colitis ka na-arụ ọrụ mgbochi mkpali dị ukwuu, na-anapụta ụmụ anụmanụ niile nọ n'òtù ọgwụgwọ site na ọnwụ n'oge DSS na-akpata colitis, na-egosi na mmetụta KPV na-eme ka ọ bụrụ na ọ dịkarịa ala na-adabere na MC1R. N'ime ụmụ anụmanụ nwere okwu MC1R nkịtị, KPV nwere ike ịkwalite mmetụta mgbochi mkpali site na iso MC1R na-emekọrịta ihe ma ọ bụ na-ahazi ụzọ mgbama mgbada ala ya.
Mmetụta mgbochi mkpali nke KPV
1. Ọrụ na eriri afọ mbufụt ụdị
Ụdị colitis na-ebute DSS: N'ime ụdị mouse colitis nke DSS, KPV gosipụtara mmetụta mgbochi mkpali dị ịrịba ama. N'ihe gbasara mgbanwe ịdị arọ, ụmụ oke ndị e ji KPV gwọọ ha nwetara ibu ha na mbụ ma ruo n'ókè ka ukwuu ma e jiri ya tụnyere ụmụ oke a na-agwọbeghị. Nleba anya n'ihe gbasara akụkọ ihe mere eme gosipụtara mbelata nke ukwuu na ntinye mkpali n'ime anụ ahụ nke ụmụ oke ndị KPV na-agwọ, kwadoro site na mbelata dị ukwuu na ọrụ myeloperoxidase (MPO). MPO bụ enzyme dị na neutrophils, na ọkwa ọrụ ya na-egosipụta oke ntinye sel mkpali na anụ ahụ. Mbelata nke ọrụ MPO na-eso ọgwụgwọ KPV na-egosi mbelata ntinye neutrophil n'ime anụ ahụ colon na nzaghachi mkpali belata. Site n'ịchọpụta okwu mRNA nke cytokines pro-inflammatory na anụ ahụ colonic, dị ka TNF-a na IL-1β, a chọpụtara na ọgwụgwọ KPV belatara ọkwa ọkwa nke cytokines pro-inflammatory. KPV wepụrụ akara ngosi colitis nke DSS kpatara site n'ọtụtụ akụkụ, gụnyere ibelata ntinye mkpụrụ ndụ mkpali, iwetu okwu mkpali, na ịkwalite mgbake dị arọ.
CD45RB(hi) ụdị mbufụt nke colon: Na CD45RB (hi) ụdị mbufụt colonic, KPV gosikwara mmetụta mgbochi mkpali dị mma. A kpalitere ihe nlereanya a site na ibufe mkpụrụ ndụ T na-egosipụta CD45RB nke ukwuu n'ime ụmụ oke na-enweghị ihe mgbochi. N'ịgbaso ọgwụgwọ KPV, ụmụ oke ndị ahụ gosipụtara mgbama mgbakasị mma, mgbake dị arọ nke nta nke nta, na nyocha akụkọ ihe mere eme gosiri mbelata mgbanwe mkpali nke eriri afọ. Otu ndị a na-emeso KPV gosipụtara mbelata ntinye mkpụrụ ndụ mkpali ma belata mmebi nrụzi crypt na anụ ahụ intestinal, na-egosi na KPV na-ebelata mbufụt eriri afọ CD45RB(hi) nke ọma ma weghachi nhazi na ọrụ eriri afọ nkịtị.
Ụdị ulcerative colitis na-ebute TNBS: N'ụdị oke ọnya na-akpata TNBS, KPV gosikwara mmetụta ọgwụgwọ dị ịrịba ama. Mgbe o nyechara KPV/SH-PGA hydrogel n'azụ oke, mgbaàmà colitis na-akawanye nke ọma. E belatara ogo nke oke ibu na oke, yana akara ọrụ ọrịa (DAI) belatara. Akara DAI na-atụle n'ụzọ zuru ezu ihe nrịbama dị ka mgbanwe n'ịdị arọ nke oke oke, njirimara fecal, na hematochesia. Mbelata ya na-egosi na KPV/SH-PGA hydrogel nwere ike ibelata ịdị njọ nke TNBS na-ebute ulcerative colitis. Ọgwụgwọ hydrogel KPV/SH-PGA na-egbochikwa mbelata eriri afọ na oke, mbelata ọkwa myeloperoxidase nke colonic, na weghachi usoro morphological colonic, gụnyere ihe mgbochi epithelial, crypts, na sel goblet na-emebibeghị. Okwu nke cytokines pro-inflammatory, TNF-α na IL-6, na anụ ahụ colonic na-ebelatakwa nke ukwuu, na-egosipụtakwa mmetụta mgbochi mkpali nke KPV na ụdị TNBS na-akpata ulcerative colitis.
Mmechi
KPV, dị ka tripeptide nwere ihe mgbochi mkpali, na-egosipụta mmetụta na-ekwe nkwa na mgbochi na ọgwụgwọ nke nsị eriri afọ na ọrịa dị iche iche metụtara mbufụt. Usoro ya na-egbochi mkpali na-agụnye ọtụtụ akụkụ, gụnyere nhazi nke ụzọ mgbaàmà ekwentị, nrụgide antioxidant, na mgbanwe nke apoptosis na autophagy.
Isi mmalite
[1] Shao W, Chen R, Lin G, et al. Na situ mucoadhesive hydrogel na-ejide tripeptide KPV: mgbochi mkpali, antibacterial na nrụzi mmetụta na chemotherapy na-ebute ọnụ mucositis[J]. Nkà mmụta sayensị biomaterials, 2021,10 (1): 227-242.DOI: 10.1039 / d1bm01466h.
[2] Sun J, Xue P, Liu J, et al. Hydrogel nke jikọrọ onwe ya nke Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV maka ibelata TNBS-Induced Ulcerative Colitis na Rats[J]. Acs Biomaterials Science & Engineering, 2021,7 (10):4859-4869.DOI:10.1021/acsbiomaterials.1c00792.
[3] Xiao B, Xu Z, Viennois E, et al. Ezubere ọnụ Ezubere Nnyefe nke Tripeptide KPV site na Hyaluronic Acid Nanoparticles arụrụ ọrụ nke ọma na-ebelata ọnya ọnya [J]. Usoro ọgwụgwọ anụ ahụ, 2017,25 (7): 1628-1640.DOI: 10.1016/j.ymthe.2016.11.020.
[4] Dalmasso G, Charrier-Hisamuddin L, Nguyen H, et al. P-078: PepT1 mediated tripeptide KPV nnabata na-ebelata mbufụt nke eriri afọ [J]. Ọrịa afọ na-ere ọkụ, 2008,14(suppl_1):S32.DOI:10.1097/00054725-200801001-00111.
[5] Kannengiesser K, Maaser C, Heidemann J, et al. KPV tripeptide enwetara Melanocortin nwere ikike mgbochi mkpali na ụdị murine nke ọrịa afọ ọzịza [J]. Ọrịa afọ na-egbuke egbuke, 2008,14 (3): 324-331.DOI: 10.1002 / ibd.20334.
Ngwaahịa dị maka naanị nyocha:
