四君子汤对UC模型大鼠的治疗作用及其对紧密连接蛋白Occludin表达的影响

目的:观察四君子汤对2,4,6-三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎大鼠治疗作用及其对黏膜上皮细胞紧密连接蛋白闭合蛋白(Occludin)表达的影响。方法:SD大鼠实验分为正常组,模型组,阳性药组(柳氮磺胺吡啶肠溶片,SASP,0.4 g·kg~(-1)),四君子汤高、中、低剂量给药组(生药5.6,2.8,1.4 g·kg~(-1)),每组8只。除正常组外,其余各组采用TNBS灌肠法制作溃疡性结肠炎模型,造模24 h后各组分别按设计剂量连续ig给药10 d。观察大鼠饮食、精神状态、疾病活动指数、大便次数与质量等情况,末次给药24 h后,处死动物取结肠,肉眼观察结肠黏膜的病变并进行结肠大体形态损伤评分,取病变部位进行HE染色,光镜下评价黏膜病理损伤指数,免疫组织化学法检测大鼠结肠Occludin蛋白的表达。结果:模型组大鼠DAI评分、结肠形态与组织学损伤评分等均比正常组高,Occludin蛋白表达较正常组低(P0.05),四君子汤与SASP治疗能不同程度减轻TNBS诱导的UC模型对黏膜的破坏,使紧密连接蛋白Occludin表达升高,抑制结肠通透性的增加,保护结肠黏膜屏障功能(P0.05)。结论:四君子汤能有效增加Occludin蛋白表达,促进实验性UC大鼠结肠黏膜屏障功能修复,这可能是其治疗结肠炎的机制之一。

Efficacy of Sijunzi Tang in TNBS-induced UC Rat Models and Effect on Occludin

Objective: To evaluate the efficacy of Sijunzi decoction in treatment of 2, 4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis and investigate its effect on expression of tight junction protein Occludin in mucosal epithelial cells. Method: SD rats were divided into normal group, model group (TNBS-induced colitis), Sijunzi Tang(SJZT) high dose group, middle dose group and low dose group (crude drug 5.6, 2.8, 1.4 g·kg^-1), and Salazosulfapyridine treatment group (SASP, 0.4 g·kg^-1), n=8 in each group(P < 0.05). Experimental ulcerative colitis models were induced by rectal instillation of TNBS in all groups except normal group. 24 h after modeling, drugs were given intragastrically continuously for ten days according to their respective doses in each group. Their diet conditions, mental state, disease activity index (DAI) scores, stool frequency and body weight were observed. 24 h after the last administration, the rats were sacrificed and their colon was taken. The pathological changes of colonic mucosa were visually observed and their scores of colon macroscopic damage index (CMDI) were recorded. Lesion areas were taken for HE staining, and colon tissues damage index (TDI) was evaluated under light microscopy,expression of Occludin proteins in colon of the rats was detected by immunohistochemical method. Result: DAI scores, CMDI scores and TDI scores in model group were higher than those in control group,Occludin protein expression was lower than in control group. However, SJZT and SASP treatment could reduce damage to mucosa of TNBS-induced UC models, increase the expression of tight junction proteins Occludin, inhibit the increase of colonic permeability, and protect the colonic mucosal barrier function(P < 0.05). Conclusion: SJZT can increase Occludin protein expression and promote the recovery of colonic mucosal barrier function in UC rats, which may be one of its mechanism for treatment of colitis.