益生菌VSL#3治疗大鼠实验性结肠炎的效果观察及对STAT1/T-bet的影响

Effect of probiotic VSL#3 in treatment of experimental colitis in rats and its influence on STAT1/T-bet

目的观察益生菌VSL#3治疗DSS诱导的大鼠实验性结肠炎的疗效及对转录因子STAT1、T-bet的影响,了解益生菌治疗实验性结肠炎的作用机制。方法采用5%DSS溶液诱导大鼠慢性溃疡性结肠炎模型,40只SD大鼠随机分为5组:正常对照组、模型组、模型+美沙拉嗪灌胃组、模型+VSL#3灌胃组、联合组(模型+VSL#3+美沙拉嗪灌胃)。采用DAI积分及组织损伤学评分检测各干预组疗效,Western blotting法检测STAT1、T-bet的表达。结果模型组大鼠DAI积分及组织病理积分明显高于正常组(P均<0.05),模型+美沙拉嗪组和模型+益生菌VSL#3组DAI评分则明显低于模型组,联合治疗组则明显低于单药治疗组,差异有显著统计学意义。与模型组比较,模型+益生菌VSL#3、模型+美沙拉嗪及联合干预后转录因子STAT1蛋白表达降低(P均<0.05);而T-bet的表达升高(P均<0.05)。其中又以联合治疗组效果最佳。结论益生菌VSL#3对大鼠实验性结肠炎有治疗作用,可抑制炎症因子的表达,其部分机制可能为通过抑制STAT1,提高T-bet的表达水平而发挥治疗作用。

Objective To investigate the therapetutie efficacy of VSL#3 against experimental colitis in rats and its effect on the expression of STAT1 and T-bet. Methods Experimental chronic ulcerative colitis in rats was induced with 5% dextran sulfate sodinm （DSS）. 40 SD rats were randomly divided into 5 groups： normal control group, model control group, model ＋ mesalamine through stomach feeding group, model ＋ probiotic VSL#3 through stomach feeding group, the combined group （model ＋ mesalamine ＋ probiotic VSL#3 through stomach feeding）. Colonic tissue damage was assessed by histopathologic score. The expression of STAT1 and T-bet were measured by Western blotting. Results Compared with the normal control group, the disease activity index and histopathologic scores were significantly increased in the model control group （both P 〈 0.05 ）. Mesalamine group and probiotic VSL#3 group could significantly reduce disease activity index and histopathologic scores compared with the model control group. The combined group was significantly lower than the monotherapy group with statistically significant difference. Moreover, the expression of STAT1 protein in probiotic VSL#3 group, mesalazine group and the combined group was also significantly decreased than that in model control group （ P 〈 0.05 ）. However, the expression of T-bet protein was elevated （ P 〈 0.05 ）. Optimum effects were achieved in the combined group. Conclusion Probiotic VSL#3 has the effect of downregulation the over expression of signaling molecule such as STAT1 and T-bet, which may be one of the mechanism of treating ulcerative colitis with probiotics.