肠愈宁对溃疡性结肠炎模型大鼠结肠黏膜损伤修复的作用研究

The study on the role of Chang Yu Ning granules in the repair of colonic mucosal injury in model rats with ulcerative colitis

[目的]研究肠愈宁对溃疡性结肠炎(UC)模型大鼠的疗效及修复结肠黏膜损伤的作用机制。[方法]将100只健康雄性SD大鼠随机分为空白对照组、模型对照组、美沙拉嗪组、肿瘤坏死因子-α(TNF-α)拮抗剂组、肠愈宁组,每组各20只。采用2,4,6-三硝基苯磺酸(TNBS)/乙醇复合法制备活动期UC大鼠模型,并分别给予肠愈宁、美沙拉嗪、益赛普进行干预。对大鼠的进食量、体重变化等一般情况进行观察,同时比较各组DAI评分。光镜下观察结肠组织病理形态学变化,酶联免疫吸附法检测大鼠血清TNF-α表达水平,Western Blot法检测结肠组织带状闭合蛋白(ZO)-1、咬合蛋白表达水平。[结果]与空白对照组比较,模型对照组DAI评分、结肠黏膜损伤评分、血清TNF-α表达水平均有显著升高(P<0.01),而咬合蛋白、ZO-1蛋白表达显著下降(P<0.01)。肠愈宁组与模型对照组比较DAI评分、结肠黏膜损伤评分、血清TNF-α表达水平均有显著下降(P<0.01),咬合蛋白、ZO-1蛋白表达显著升高(P<0.01)。[结论]肠愈宁可下调UC模型大鼠血清TNF-α水平,并上调结肠组织紧密连接(TJ)关键蛋白咬合蛋白、ZO-1的表达,修复结肠黏膜损伤,而进一步治疗UC。

[Objective]To study the effect of Chang Yu Ning Granules on the model rats with ulcerative colitis(UC)and the mechanism of repairing colonic mucosal injury.[Methods]One hundred healthy male Sprague-Dawley rats were randomly divided into blank control group,model control group,mesalazine group,tumor necrosis factor-α(TNF-α)antagonist group and Chang Yu Ning Granules,with 20 rats in each group.The active UC rat models were prepared by 2,4,6-trinitro-benzen-sulfonic acid(TNBS)/ethanol composite method,and were intervened using Chang Yu Ning Granules,Mesalazine and Etanercept.The general conditions of the rats such as food intake,body weight changes,etc.were observed,and the DAI scores of each group were compared.The histopathological changes of colon tissue were observed under light microscope.The expression of TNF-α in serum was detected by enzyme-linked immunosorbent assay(ELISA).The expression level of zonal occluden(ZO)-1 and occludin of colon tissue were detected by Western Blot method.[Results]Compared with the blank control group,the DAI score,colonic mucosal injury score and serum TNF-α expression in the model control group were significantly increased(P<0.01),while the expression of occludin and ZO-1 protein was significantly decreased(P<0.01).Compared with the model control group,the DAI score,colonic mucosal injury score and serum TNF-α expression level in the Chang Yu Ning Granules group were significantly decreased(P<0.01),and the expression of occludin and ZO-1 protein was significantly increased(P<0.01).[Conclusion]Chang Yu Ning Granules may down-regulating the serum TNF-α level in UC model rats and increase the expression of tight junction protein occludin and ZO-1 in the colon tissue,thereby repairing colonic mucosal injury and further treating UC.