奥曲肽治疗TNBS致大鼠溃疡性结肠炎及其机制研究  

Treatment of ulcerative colitis induced by TNBS with octreotide in rats and its mechanism

作　　者：朱锐 何灵 唐瑶[1] 白杰[1] ZHU Rui;HE Ling;TANG Yao;BAI Jie(Dept of Pharmacology,School of Pharmacy,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学药学院药理学教研室,新疆乌鲁木齐830011

出　　处：《中国药理学通报》2020年第9期1276-1281,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金地区科学基金资助项目(No 81360071);新疆维吾尔自治区自然科学基金资助项目(No 2019D01C195);自治区“十三五”重点学科资助。

摘　　要：目的研究三硝基苯磺酸诱导SD大鼠致溃疡性结肠炎后,奥曲肽对其的治疗作用,并探讨奥曲肽对溃疡性结肠炎以及结肠粘膜炎症的免疫机制。方法70只SD大鼠随机分为四组,除正常对照组,其余各组用5%三硝基苯磺酸溶液灌肠建立溃疡性结肠炎模型。造模24 h后,奥曲肽给药组(50μg·kg^-1·d^-1,ip)干预7 d,模型组、正常对照组给予等量生理盐水,阳性药组灌胃给予柳氮磺胺吡啶。分别计算DAI、CMDI以及TDI评分;酶联免疫吸附法检测结肠组织匀浆中的IL-6、IL-8、IL^-1β、TNF-α、PLA2;免疫组化和Real time-PCR观察PI3K、AKT1表达水平。结果与模型组相比,奥曲肽组大鼠组织匀浆中各细胞因子表达水平均明显降低。免疫组化和Real time-PCR结果显示,与模型组相比,奥曲肽组PI3K、AKT1表达明显下降。结论奥曲肽可能通过PI3K、AKT1途径,发挥其抑制免疫,减轻炎症的作用,从而达到治疗溃疡性结肠炎的目的。Aim To study the therapeutic effect of octreotide on trinitrobenzenesulfonic acid(TNBS)-induced ulcerative colitis(UC)in SD rats,and to explore the immune mechanism of octreotide on UC and colonic mucosal inflammation.Methods Seventy SD rats were randomly divided into four groups.Except the normal group,the remaining groups were enema with 5%TNBS solution to establish UC model.24 hours after modeling,the octreotide group(50μg·kg^-1·d^-1,ip)intervened for 7 days.The model group and the normal group were given the same amount of normal saline,and the positive drug group was given sulfasalazine by gavage.The scores of DAI,CMDI and TDI were calculated respectively.IL-6,IL-8,IL^-1β,TNF-α,PLA2 in colon tissue homogenate were detected by enzyme linked immunosorbent assay.PI3K,AKT expression levels were observed by immunohistochemistry and real time-PCR.Results Compared with model group,the expression level of cytokines in tissue homogenate of octreotide group was significantly reduced.Immunohistochemistry and real time-PCR results showed that compared with model group,the expression of PI3K and AKT in octreotide group decreased significantly.Conclusions Octreotide may exert its inhibitory immunity and reduce inflammation through the PI3K,AKT1,and p-AKT1 pathways,so as to achieve the purpose of treating ulcerative colitis.

关 键 词：溃疡性结肠炎 TNBS 奥曲肽 结肠 PI3K AKT1 

分 类 号：R-332[医药卫生] R322.45