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Protective Effect Of Octreotide On Rats With TNBS Induced Ulcerative Colitis And Its Mechanism

Posted on:2021-03-24Degree:MasterType:Thesis
Country:ChinaCandidate:R ZhuFull Text:PDF
GTID:2404330602462868Subject:Pharmaceutical
Abstract/Summary:PDF Full Text Request
Objective: To study the therapeutic effect of octreotide on trinitrobenzenesulfonic acid(TNBS)induced ulcerative colitis(UC)in Sprague-Dawly(SD)rats,and to explore the immune mechanism of octreotide on UC and colon mucosal inflammation.Methods: 70 male and female SD rats randomly divided into 4 groups: normal group,model group,octreotide group,and positive drug group(salazosulfapyridine group,SASP).Except the normal control group,the remaining groups were enema with 5% TNBS(90mg/kg)solution to establish UC model.24 hours after modeling,the octreotide group(50 ?g/kg/d,i.p.)intervened for 7 days,the model group and the normal group were given an equal volume of saline for 7 days,and the SASP group(0.4 g/kg/d)was gavaged.Observe and evaluate the histological damage of the colonic mucosa,calculate the DAI,CMDI and TDI scores;ELISA to detect IL-1?,IL-6,IL-8,TNF-?,PLA2;Immunohistochemical experiment to observe the quantitative expression and expression site of PI3 K,AKT1,P-AKT1,JNK2 protein.The mRNA expression levels of PI3 K,AKT,c-Jun and JNK were measured by Real time-PCR method.Results: Compared with the model group,the colonic lesions in the octreotide group were significantly improved,and the TDI score was significantly reduced(P <0.01);the levels of IL-1?,IL-6,IL-8,TNF-? and PLA2 in the tissue homogenate The expression level was significantly reduced,and the difference was statistically significant(P <0.01).Immunohistochemical results showed that compared with the model group,PI3 K,AKT1,P-AKT1,JNK2 protein expression in the octreotide group was significantly reduced,with statistical differences(P <0.01).Real time-PCR experiment results showed that compared with the model group,PI3 K,AKT,c-Jun,JNK mRNA expression levels decreased,the difference was statistically significant(P <0.05).Conclusion: Octreotide may exert its inhibitory immunity and reduce inflammation through PI3 K,AKT1,c-Jun and JNK signaling pathways,so as to achieve the purpose of treating ulcerative colitis.
Keywords/Search Tags:Ulcerative colitis, TNBS, octreotide, PI3K, JNK
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