甘草酸二铵对溃疡性结肠炎大鼠Foxp3 mRNA表达的影响

Diammonium glycyrrhizinate up-regulates the expression of Foxp3 mRNA in rats with ulcerative colitis

目的:研究甘草酸二铵(DG)对大鼠溃疡性结肠炎(UC)的疗效及对大鼠外周血单个核细胞中Foxp3 mRNA表达的影响,继而从自身免疫方面探讨DG治疗大鼠UC的作用机制.方法:用2,4,6-三硝基苯磺酸(TNBS)/乙醇灌肠复制大鼠UC模型,健康雌性SD大鼠随机分为正常对照组、模型组、DG组[40mg/(kg·d)],每组10只.造模10d后,收集标本,观察大鼠疾病活动指数(DAI)、组织学改变,应用RT-PCR半定量检测大鼠外周血单个核细胞中Foxp3 mRNA的表达水平.结果:正常对照组、模型组和DG组的DAI评分分别为0.3±0.6,7.1±0.2,3.1±0.6;组织学损伤评分分别为0.9±0.2,6.7±0.5,3.3±0.4,与正常对照组相比,DG组、模型组上述指标评分均显著增高(P<0.05);而与模型组相比,DG组能显著改善UC症状(P<0.05).模型组大鼠Foxp3 mRNA水平低于正常组(0.51±0.34vs1.09±0.38,P<0.05);与模型组相比,DG组Foxp3 mRNA的表达显著升高(0.92±0.53vs0.51±0.34,P<0.05).结论:DG可显著改善大鼠UC,通过上调外周血单个核细胞中Foxp3 mRNA的表达抑制自身反应性T淋巴细胞的增殖可能是其机制之一.

AIM：To evaluate the protective effect of diammonium glycyrrhizinate（DG） against ulcerative colitis in rats and to investigate potential mechanisms involved.METHODS：Thirty Sprague-Dawley（SD） rats were equally randomized into normal control group,model group and DG group.Ulcerative colitis was induced in the DG group and model group by rectal administration of trinitrobenzene sulphonic acid（TNBS）.Disease activity index（DAI） and histological damage were evaluated,and the expression of forkhead box P3（Foxp3） mRNA in peripheral blood mononuclear cells（PBMCs） was detected by reverse transcriptionpolymerase chain reaction（RT-PCR）.RESULTS：Both DAI and histological damage score were significantly higher in the model group than in the normal control group（DAI：7.1 ± 0.2 vs 0.3 ± 0.6,P〈0.05;histological damage score：6.7 ± 0.5 vs 0.9 ± 0.2,P〈0.05）.Compared with the model group,DAI and histological damage score were significantly improved in the DG group（DAI：3.1 ± 0.6 vs 7.1 ± 0.2,P〈0.05;histological damage score：3.3 ± 0.4 vs 6.7 ± 0.5,P〈0.05）.Compared with the normal control group,the expression of Foxp3 mRNA was down-regulated in PBMCs in the model group（0.51 ± 0.34 vs 1.09 ± 0.38,P〈0.05）.DG treatment significantly up-regulated the expression of Foxp3 mRNA in PBMCs（0.92 ± 0.53 vs 0.51 ± 0.34,P〈0.05）.CONCLUSION：DG can ameliorate colonic inflammation in rats with ulcerative colitis possibly by increasing the expression of Foxp3 mRNA in PBMCs.