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作 者:周梓琪 李剑 刘丹 吴洁[1] ZHOU Ziqi;LI Jian;LIU Dan;WU Jie(School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198;Jinling Pharmaceutical Co.,Ltd.,Nanjing 210009,China)
机构地区:[1]中国药科大学生命科学与技术学院,南京211198 [2]金陵药业股份有限公司,南京210009
出 处:《中国药科大学学报》2023年第1期107-114,共8页Journal of China Pharmaceutical University
基 金:国家自然科学基金资助项目(No.81973224)。
摘 要:探讨术苓健脾胶囊(术苓)对2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠实验性结肠炎的作用及其机制。采用2.5%TNBS灌肠制备大鼠实验性结肠炎模型。将大鼠随机分为正常组、模型组、肠炎宁(180 mg/kg)组以及术苓低剂量(40 mg/kg)、高剂量(120 mg/kg)组。造模后药物治疗7 d后处死大鼠。其间每日记录大鼠体重,观察大鼠疾病活动状态。实验结束后,取结肠组织进行HE病理学分析、检测结肠组织中髓过氧化物酶(MPO)酶活、诱导型一氧化氮合酶(iNOS)、炎性细胞因子(IL-6、IL-1β、IFN-γ、IL-10)及紧密连接蛋白(occludin、ZO-1)的表达水平,并检测血清中炎性细胞因子(IL-6、IL-1β)的含量。结果表明,与模型组相比,术苓给药显著缓解了TNBS造模引起的体重下降、疾病活动指数(DAI)升高,缓解了结肠组织的缩短、水肿以及病理学损伤,减少了炎性细胞浸润、隐窝的破坏与杯状细胞的丢失,降低了结肠组织MPO酶活性、iNOS与炎性细胞因子的水平,增加了结肠紧密连接蛋白的表达,同时降低了血清中的炎性因子的含量。结果表明,术苓通过降低炎性因子水平,增加肠道紧密连接蛋白的表达,改善TNBS诱导的大鼠实验性结肠炎。本研究为术苓的临床应用提供了理论依据。To investigate the pharmacodynamic effects and mechanism of Zhuling Jianpi capsule(Zhuling)on 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis in rats.The experimental colitis model was established by enema with 2.5%TNBS.The rats were randomly divided into normal group,model group,Changyanning(180 mg/kg)group and Zhuling low-dose(40 mg/kg)group and Zhuling high-dose(120 mg/kg)group.After modeling,the rats were executed after 7 days of drug treatment.During this period,the disease activity status of the rats was observed,and the body weights of the rats were recorded daily.At the end of the experiment,the colonic tissues were obtained for the analysis of the expression of hematoxylin-eosin(HE)staining.The myeloperoxidase(MPO)enzyme activity,mRNA expression levels of inducible nitric oxide synthase(iNOS)and inflammatory cytokines(IL-6,IL-1β,IFN-γ,IL-10)were determined,and the levels of intestinal tight junction proteins and serum inflammatory factor levels were measured.The results showed that compared with model group,the administration of Zhuling significantly alleviated the weight loss and elevated the disease activity index(DAI)caused by TNBS,relieved the shortening,edema and pathological damage of colonic tissue,reduced inflammatory cell infiltration,destruction of crypt and loss of goblet cells,decreased the MPO enzyme activity of colonic tissue,iNOS and pro-inflammatory cytokines in colon,increased the levels of colonic tight junction protein(occludin,ZO-1),and decreased serum levels of inflammatory factors(IL-6,IL-1β).The results suggest that Zhuling administration ameliorates TNBS-induced experimental colitis in rats by decreasing the level of inflammatory factors and increasing the expression of intestinal tight junction proteins.This experiment could provide a theoretical basis for the clinical application of Zhuling.
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