奇任醇通过抑制炎症细胞因子和诱导淋巴细胞凋亡减轻小鼠溃疡性结肠炎（英文）

Kirenol relieves dextran sulfate sodium-induced ulcerative colitis in mice by inhibiting inflammatory cytokines and inducing CD4^+T lymphocyte apoptosis

目的研究奇任醇在葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)发生和发展中的作用。方法将C57BL/6小鼠随机分为UC+双蒸水灌胃组和UC+奇任醇治疗组。所有小鼠连续7 d在饮水中加入DSS建立UC模型,第0天到第7天双蒸水或奇任醇灌胃给药。每日观察小鼠体质量、直肠出血和粪便性状等临床指标并进行疾病活动度指数评分(DAI)。7 d后处死小鼠,观察结肠组织形态和长度,行组织病理学分析。取肠系膜淋巴结制成单细胞悬液并体外用抗CD3和抗CD28刺激活化,分析细胞培养上清中分泌的细胞因子IFN-γ、IL-17A、IL-6和TNF-α的含量,流式细胞术检测肠系膜淋巴结细胞的凋亡百分比。结果奇任醇可以抑制DSS诱导的溃疡性结肠炎的发生发展,减轻结肠损伤,抑制炎症细胞因子的分泌,诱导淋巴细胞的凋亡。结论奇任醇可以缓解DSS诱导的溃疡性结肠炎,这种作用可能与抑制炎症细胞因子分泌和诱导炎性淋巴细胞凋亡有关。

Objective To investigate whether kirenol,the major pharmacologically active compound of the Chinese medicinal herb Herba Siegesbeckiae,can protect mice from dextran sulfate sodium(DSS)-induced ulcerative colitis(UC).Methods C57 BL/6 mice with or without kirenol pretreatment were treated with DSS in drinking water for 7 days to induce UC.The symptoms of UC including weight loss,diarrhea and bloody stool were observed daily and graded using the disease activity index(DAI).Colon injury of the mice was assessed by measuring the length of the colon and HE staining of the colon tissue.The levels of inflammatory cytokines produced by the mesenteric lymph nodes(MLNs)lymphocytes were measured using enzyme-linked immunosorbent assay;the apoptosis of the lymphocytes and CD4^+T cells was analyzed using flow cytometry.Results The mice receiving pretreatment with kirenol showed obviously ameliorated symptoms of UC and milder pathological changes in the colon as compared with the control mice.Kirenol treatment significantly down-regulated the secretion of IFN-γ,IL-17 A,IL-6 and TNF-αby the MLNs lymphocytes and increased the apoptosis of lymphocytes,especially CD4^+T cells in the DSS-treated mice.Conclusion Kirenol can protect against T cell-mediated colon injury in DSS-treated mice possibly by suppressing the secretion of inflammatory mediators and inducing apoptosis of the inflammatory lymphocytes.