目的 探讨山姜素对葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠的保护作用及其作用机制。方法 C57BL/6小鼠随机分为对照组、模型组和25、50、100 mg/kg山姜素组。模型组和治疗组每天给予3%葡聚糖硫酸钠溶液，连续7 d。治疗组每日ip生理盐水0.5 mL+25、50、100 mg/kg山姜素，对照组和模型组每天ip生理盐水0.5 mL，连续7 d。观察小鼠体质量变化、结肠长度、疾病活动指数（DAI）评分、组织学损伤评分等炎症反应；透射电镜观察肠上皮细胞间连接；免疫组织化学法、Western blotting法检测肠道紧密连接蛋白claudin-2、occludin、ZO-1、STAT3、pSTAT3、IL-6的表达和STAT3/IL-6信号通路的表达情况。结果 与模型组比较，山姜素能够显著缓解小鼠体质量减轻和肠管缩短，降低DAI和组织学评分。山姜素可增强小鼠肠黏膜occludin、ZO-1表达，减弱claudin-2表达，并能够抑制STAT3/IL-6信号通路。结论 山姜素能够上调葡聚糖硫酸钠诱导的溃疡性结肠炎小鼠结肠组织occludin、ZO-1的表达，下调claudin-2的表达，通过调节紧密连接蛋白的表达，保护肠上皮细胞屏障的完整性和通透性。通过抑制IL-6/STAT3通路，减轻结肠炎症反应。

Objective To study the protective effect of alpinetin on dextran sulfate sodium-induced ulcerative colitis in mice and explain its mechanism. Methods C57BL/6 mice were divided into control group, model group, and apinetin (25, 50, and 100 mg/kg) groups. Mice in model and apinetin groups were given 3% dextran sodium sulfate solution for 7 d. Mice in apinetin groups were ip administered with normal saline 0.5 mL + 25、50、100 mg/kg apinetin, while mice in control and model group were ip administered with normal saline 0.5 mL for 7 d. The body weight, intestinal length, disease activity index (DAI), and histological scores were observed. Epithelial tight junctions were observed by transmission electron microscope. Expression of tight junction claudin-2, occluding, ZO-1, STAT3, pSTAT3, IL-6 in mice and STAT3/IL-6 signaling pathway in the colon were determined by immunohistochemical method and Western blotting method. Results Compared with model group, alpinetin could significantly alleviate body weight loss and intestinal length shortening in mice, reduced DAI and histological scores. In the same time, alpinetin could enhance the expression of occludin and ZO-1 in intestinal mucosa, attenuate claudin-2 expression, and inhibit STAT3/IL-6 signaling pathway. Conclusion Alpinetin can up-regulate the expression of occludin and ZO-1 in the colon tissue of dextran sulfate sodium-induced ulcerative colitis in mice, down regulate the expression of claudin-2, and protect the integrity and permeability of the intestinal epithelial cell barrier by regulating the expression of tight junction. Alpinetin can reduce the colonic inflammatory reaction by inhibiting STAT3/IL-6 signaling pathways.

辽宁省自然科学基金资助项目（20170540529）