雷公藤多甙对实验性结肠炎大鼠Th17/Treg细胞分化和平衡的影响

Effect of Tripterygium Glycosides on Differentiation and Balancing of Th17/Treg Cells in Rats With Experimental Colitis

背景:免疫因素在炎症性肠病(IBD)的发病机制中起重要作用。临床研究显示雷公藤多甙对IBD有良好疗效。目的:探讨雷公藤多甙对实验性结肠炎大鼠Th17/Treg细胞分化和平衡的影响。方法:建立TNBS-乙醇结肠炎大鼠模型,分别予0.9%NaCl溶液(模型组)、雷公藤多甙和美沙拉嗪灌胃干预,2周后行疾病活动指数(DAI)和结肠黏膜损伤评估。提取各组肠系膜淋巴结单个核细胞,采用ELISA法检测上清液中的Th17/Treg相关细胞因子水平。采用免疫组化法检测结肠组织促炎细胞因子表达。结果:模型组大鼠结肠炎症状较重,DAI评分以及黏膜损伤大体和组织学评分显著高于雷公藤多甙组和美沙拉嗪组(P<0.05),两种药物对结肠炎症的改善作用无明显差异(P>0.05)。与模型组相比,美沙拉嗪组和雷公藤多甙组肠系膜淋巴结单个核细胞上清液中的IL-23、TNF-α水平显著降低(P<0.05),雷公藤多甙还可降低IL-6水平(P<0.05)。美沙拉嗪组TGF-β水平显著高于雷公藤多甙组(P<0.05);两种药物对IFN-γ水平均无影响(P>0.05)。美沙拉嗪可显著下调结肠组织IL-6表达(P<0.05)。结论:抑制Th17细胞分化、促进Treg细胞分化以调节Th17/Treg失衡可能是雷公藤多甙对IBD的治疗机制之一。

Background:Immune factors play an important role in the pathogenesis of inflammatory bowel disease(IBD).Clinical studies have shown that tripterygium glycosides is effective for the treatment of IBD.Aims:To investigate the effect of tripterygium glycosides on differentiation and balancing of Th17/Treg cells in rats with experimental colitis.Methods:Experimental colitis was induced by TNBS-ethanol method in rats to evaluate the therapeutic effect of tripterygium glycosides.After intragastrically administered with normal saline(model group),tripterygium glycosides or mesalazine,respectively once a day for two weeks,the disease activity index(DAI)was assessed,and the colonic mucosal injury was examined macro-and microscopically.Mononuclear cells of mesenteric lymph nodes were extracted,and the levels of Th17/Treg-related cytokines in the supernatant were detected by ELISA method.The expression of proinflammatory cytokines in colon tissues was detected by immunohistochemistry.Results:The symptoms of experimental colitis were more severe in model group.DAI,gross morphological and histopathological score of colonic mucosal injury were significantly higher in model group than in tripterygium glycosides and mesalazine groups(P<0.05),while the therapeutic effect of tripterygium glycosides was identical to that of mesalazine(P>0.05).Compared with the model group,the levels of IL-23 and TNF-αin the supernatant of mesenteric lymph nodes mononuclear cells in mesalazine group,and the levels of IL-23,TNF-αand IL-6 in tripterygium glycosides group were significantly reduced(P<0.05).The level of TGF-βwas higher in mesalazine group than in tripterygium glycosides group(P<0.05).No significant changes were observed in level of IFN-γin all the three groups(P>0.05).In rats treated with mesalazine,the expression of IL-6 in colon tissues was down-regulated significantly(P<0.05).Conclusions:Tripterygium glycosides have the potential to inhibit the differentiation of Th17 cells and promote the differentiation of Treg cells in IBD.Regulating the imbalance of Th17/Treg cells might be one of the mechanisms of its therapeutic effect on IBD.