白藜芦醇对溃疡性结肠炎小鼠肠黏膜细胞因子表达的影响

Effect of Resveratrol on Cytokines Expression in Colonic Mucosa of Mice with Ulcerative Colitis

目的探讨白藜芦醇(Resveratro)l对溃疡性结肠炎(UC)治疗的可能机制。方法采用葡聚糖硫酸钠(Dextran sulfate Sodium,DSS)制作UC小鼠模型,小鼠随机分4成组:正常对照(NC)组、模型(MD)组、低剂量(RLD)、高剂量(RHD)白藜芦醇治疗组。造模7d同时给予干预治疗,停用造模药物并后续治疗7d。记录分析疾病活动指数(DAI),14d后处死小鼠,取结肠行HE染色;利用实时荧光定量RT-PCR法检测IL-10、TNF-α、IL-6和IL-1βmRNA的表达,ELISA法测小鼠肠黏膜IL-10、TNF-α、IL-6和IL-1β蛋白水平。结果低、高剂量白藜芦醇治疗组小鼠第5～14天DAI明显低于模型组(P<0.05);模型组IL-10表达明显低于正常组(P<0.05),其TNF-α、IL-6和IL-1βmRNA和蛋白表达则高于正常组(P<0.05);低、高剂量白藜芦醇治疗组结肠IL-10mR-NA表达和蛋白水平明显高于模型组(P<0.05),其TNF-α、IL-6和IL-1βmRNA和蛋白水平则低于模型组(P<0.05);高剂量白藜芦醇治疗组IL-10mRNA表达和蛋白水平明显高于低剂量组(P<0.05),其TNF-α、IL-6和IL-1βmRNA和蛋白水平则低于低剂量组(P<0.05)。结论白藜芦醇可以提高抗炎细胞因子IL-10的水平并降低致炎细胞因子TNF-α、IL-6和IL-1β的水平,通过抗炎和降低肠道过度的免疫反应,对UC发挥治疗作用。

Objective To investigate the therapeutic mechanism of resveratrol for the treatment of ulcerative colitis （UC） .Methods Ulcerative colitis was induced in mice by oral administration of synthetic dextran sulfate sodium for 7 days,and intervention treatment with resveratrol was carried out simultaneously during the modeling,the treatment lasting another 7 days.Mice were divided into normal control （NC） group,colitis model （MD） group,low-dose resveratro （lLDR） group,and high-dose resveratro （lHDR） group.Disease activity index was recorded.After treatment,IL-10,TNF-α,IL-6,IL-1β mRNA expression levels in the colonic tissue were detected with qRT-PCR and their protein expression were determined by ELISA.Results Colonic IL-10 mRNA and protein expression decreased significantly in MD group compared with NC group （P〈0.05） ,and increased in the LDR and HDR groups in comparison with MD group （P〈0.05） from the 5th to 14th day of treatment.The mRNA expression levels and protein of TNF-α,IL-6 and IL-1βin colonic tissue were significantly increased in the MD group （P〈0.05 compared with the NC group）,and decreased in the LDR and HDR groups （P〈0.05 compared with MD group） .Conclusion Resveratrol shows certain therapeutic effect on UC by inhibiting the colonic inflammation and regulating immune function through up-regulating IL-10 expression and down-regulating TNF-α,IL-6,IL-1β expression.