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目的:研究熊果酸(UA)对葡聚糖硫酸钠(DSS)诱导的实验性小鼠结肠炎模型的抗炎作用,旨在阐明其对肠上皮细胞(IEC)作用的可能分子机制.方法:在体内研究中,将体质量为20～22 g 的雄性BALB/c 小鼠15只采用随机数字表法分为正常对照组、DSS模型组、DSS+熊果酸治疗组.通过3％DSS诱导8 d,制备小鼠结肠炎模型;其中一组D S S 诱导的小鼠结肠炎模型采用UA 预处理.各实验组的小鼠体质量和结肠长度分别采用物理天平和游标卡尺测定;参照临床疾病活动指数(DAI)评分法对小鼠进行评分.采用HE 染色观察各组结肠组织病理学变化;通过ELISA 法测定各组小鼠血液中血清淀粉样蛋白酶A 和结肠组织中IL-6的水平.以IL-6 刺激分化的Caco-2 细胞制备体外人肠上皮细胞炎症模型,通过Western blot检测UA 对肠上皮细胞IL-6/STAT3 信号通路中STAT3磷酸化的影响.结果:①与正常对照组比较,DSS 模型组的DAI评分增加、结肠长度缩短和组织损伤明显,差异均具有统计学意义(P＜0.0 5);与D S S 模型组比较,UA 显著抑制了 DSS 诱导的DAI 评分增加、结肠长度缩短和组织学损伤,差异均具有统计学意义(P＜0.05).②与正常对照组比较,DSS 模型组的血清淀粉酶(SAA)水平和结肠组织中IL-6 水平升高明显,差异均具有统计学意义(P＜0.05);与DSS 模型组比较,UA 可显著逆转DSS 诱导的血清淀粉酶(SAA)水平和结肠IL-6 水平的升高,差异均具有统计学意义(P＜0.05).③与正常肠上皮细胞比较,IL-6刺激显著上调STAT3的磷酸化水平;而UA 可显著抑制肠上皮细胞中IL-6 诱导的STAT3 磷酸化水平的增加,差异具有统计学意义(P＜0.05).结论:熊果酸可通过阻断IL-6/STAT3 信号通路改善了 DSS 诱导的结肠炎,提示熊果酸在靶向治疗溃疡性结肠炎中可能具有临床应用潜力.“,”Objective:Anti-inflammatory effects of ursolic acid(UA)on a dextran sulfate sodium(DSS)-in-duced experimental murine colitis models was investigated to elucidate its possible molecular mechanisms on in-testinal epithelial cells(IEC).Methods:For in vivo study,a total of 15 male BALB/c mice weighing(20-22)g were randomly divided into three groups:normal control group,DSS model group and DSS+UA treatment group;the mouse colitis model was induced by 3％dextran sodium sulfate(DSS)for 8 days;one of the DSS-in-duced groups was pretreated with UA.The body weight and colon length of mice in each group were measured by physical balance and vernier caliper,respectively.The mice in each group were scored according to the clini-cal disease activity index(DAI)score method.HE staining was used to observe the histopathological changes of colon in each group.The changes of serum amyloid protease A(SAA)and IL-6 expression in colon tissue were measured by ELISA.Using IL-6-stimulated differentiated Caco-2 cells as an in vitro inflammatory model of hu-man intestinal epithelium,the effects of UA on the activation of IL-6/signal transducer and activator of transcrip-tion 3(STAT3)signal pathway in IEC were examined by Western blot for STAT3 phosphorylation.Results:1)Compared with the normal control group,the DAI score was increased,the length of the colon was shortened,and the histological damage was obvious in the DSS model group(P＜0.05);administration of UA significantly reduced the severity of DSS-induced murine colitis as assessed by DAI score,colon length,and histology damage of colon(P＜0.05).2)Compared with the normal control group,the SAA level and the IL-6 level of colon tissue in the DSS model group increased significantly.The DSS-induced increases of SAA and colonic IL-6 levels were reversed by UA treatment(P＜0.05).3)Compared with normal IEC,IL-6 stimulation significantly increased the phosphorylation level of STAT3;STAT3 phosphorylation in IEC-treated with IL-6 and UA was significantly in-hibited compared with only IL-6 stimulation(P＜0.05).Conclusion:Our findings implicate that UA ameliorates DSS-induced colonic inflammation by blocking IL-6/STAT3 signaling pathway,and therefore indicate that UA may have clinical potential as a novel targeted therapy for ulcerative colitis.