辣椒素通过肠道菌群改善DSS诱导的小鼠结肠炎

Capsaicin ameliorates DSS-induced colitis in mice by affecting gut microbiota

目的 探讨不同剂量的辣椒素对小鼠溃疡性结肠炎肠道炎症和肠道菌群的影响。方法 将25只清洁级6~8周龄C57小鼠随机分为正常对照组、葡聚糖硫酸钠(DSS)组、辣椒素(5 mg/kg CAP)+DSS组、辣椒素(10 mg/kg CAP)+DSS组、辣椒素(20 mg/kg CAP)+DSS组,每组5只。通过自由饮用3%DSS水诱导小鼠结肠炎模型。在DSS干预前7 d,每天给予200μL相应剂量的辣椒素灌胃,至干预的第8天处死。观察记录小鼠体质量、疾病活动指数(DAI)、测量结肠长度;利用实时荧光定量聚合酶链式反应(RT-qPCR)和蛋白印迹(WB)检测结肠组织的炎症因子及肠道屏障的基因转录水平以评估辣椒素对结肠炎小鼠的作用;并通过粪便16S rRNA测序检测小鼠肠道菌群。结果 辣椒素在一定范围内,成剂量依赖性改善小鼠肠炎大体,下调促炎症因子IL-6、IL-18的表达,增强肠道屏障ZO-1、MUC2、Tff3、Occludin的表达;并可重塑肠炎肠道菌群组成,改变菌群相对物种丰富度。结论 辣椒素在合适的剂量范围内可有效改善小鼠结肠炎,并调整小鼠肠道菌群结构。

Objective To investigate the effects of different doses of capsaicin on intestinal inflammation and intestinal flora in mice with ulcerative colitis. Methods Twenty-five specific pathogen-free C57 mice aged 6-8 weeks were randomly divided into control group, dextran sulfate sodium(DSS) group, capsaicin(5mg/kg CAP) + DSS group, capsaicin(10 mg/kg CAP) +DSS group, capsaicin(20 mg/kg CAP) +DSS group, with 5 mice in each group. The colitis model was induced by drinking 3% DSS water. Before the DSS intervention 7th day, 200 μL of capsaicin was given by gavage every day until the 8th day of the intervention. Body weight, disease activity index(DAI), and colon length were calculated;real-time quantitative polymerase chain reaction(RT-qPCR) and Western Blot(WB) were used to detect the gene transcription level of inflammatory factors and mucosal barrier to evaluate the effect of capsaicin in colitis, and the effect of capsaicin on gut microbiota in mice was determined by fecal and detect the gut microbiota in mice by 16S rRNA sequencing of feces. Results Capsaicin, within a certain range, dose-dependently ameliorated intestinal inflammation in mice, down-regulated the expression of pro-inflammatory factors IL-6, IL-18, enhanced the expression of intestinal barrier ZO-1, MUC2, Tff3, Occludin, and reshaped the composition of gut microbiota of intestinal inflammation, resulting in changes in the relative species richness of gut microbiota. Conclusion Capsaicin effectively ameliorates colitis and adjusts the gut microbiota structure in mice in the appropriate dose range.