邓钧?曾丽珊?刘乐?陈烨?

【摘要】 目的 探讨二甲双胍与美沙拉嗪在治疗小鼠结肠炎中的疗效差异性。方法 选取6 ～ 8周龄的C57BL/6雄性小鼠32只，随机分为Control组、硫酸葡聚糖（DSS）组、DSS+美沙拉嗪组、DSS+二甲双胍组，每组8只。Control组小鼠自由饮用高压灭菌双蒸水，并每日予0.2 ml 磷酸盐缓冲液（PBS）灌胃。采用3%DSS诱导C57BL/6雄性小鼠结肠炎模型。DSS组小鼠自由饮用3%DSS溶液，每日予0.2 ml PBS灌胃，DSS+美沙拉嗪组、DSS+二甲双胍组自由饮用3%DSS溶液，予100 mg/（kg·d） 的美沙拉嗪或100 mg/（kg·d） 二甲双胍灌胃。评估各组小鼠体质量变化、结肠长度、疾病活动指数、组织病理学改变及肠道炎症因子表达情况。结果 与DSS组相比，DSS+二甲双胍与DSS+美沙拉嗪组均可降低小鼠结肠炎所致的体质量丢失、疾病活动度评分、组织病理学评分及肠道炎症因子表达水平（P均< 0.05），但DSS+二甲双胍组与DSS+美沙拉嗪组上述指标比较差异均无统计学意义（P均> 0.05）。结论 二甲双胍可以减轻DSS诱导的小鼠结肠炎，其疗效不亚于美沙拉嗪。

【关键词】 结肠炎;二甲双胍;美沙拉嗪;疗效

Comparison of efficacy between metformin and mesalazine in treatment of experimental colitis in mouse models Deng Jun， Zeng Lishan， Liu Le， Chen Ye. Department of Gastroenterology， the Sixth Affiliated Hospital of Sun Yat-sen University， Guangzhou 510655， China

Corresponding author， Chen Ye， E-mail： yechen@ smu. edu. cn

【Abstract】 Objective To compare the efficacy between metformin and mesalazine in the treatment of experimental colitis in mouse models. Methods Thirty-two C57BL/6 male mice aged 6-8 weeks were randomly divided into the control， dextran sulphate sodium （DSS）， DSS+mesalazine and DSS+metformin groups， with 8 animals in each group. In the control group， the animals were given ad libitum access to autoclaved double-distilled water and oral gavage of 0.2 ml PBS daily. C57BL/6 male mouse models were induced by 3% DSS. In the DSS group， the mice were given ad libitum access to 3% DSS and oral gavage of 0.2 ml PBS daily. In the DSS+mesalazine and DSS+metformin groups， the animals were given ad libitum access to 3% DSS， and oral gavage of 100 mg/（kg·d） mesalazine or metformin. The body weight， colon length， disease activity index （DAI）， histopathological changes and the expression levels of pro-inflammatory cytokines were evaluated in each group. Results Compared with the DSS group， mice treated with DSS+metformin or DSS+mesalazine experienced significantly less body weight loss，lower DAI scores， lower histopathological scores and lower expression levels of pro-inflammatory cytokines（all P < 0.05）. No significant difference was noted between the metformin and mesalazine groups（all P > 0.05）. Conclusion Metformin can ameliorate DSS-induced experimental colitis in mice， which yields equivalent efficacy to that of mesalazine.

【Key words】 Colitis;Metformin;Mesalazine;Efficacy

潰疡性结肠炎（UC）一种以腹痛、腹泻和黏液血便为表现的慢性非特异性肠道疾病。UC目前尚无有效治愈药物，临床上常用的治疗药物包括氨基水杨酸制剂、糖皮质激素、免疫抑制剂和生物制剂。UC病程易反复迁延，严重影响患者身心健康和生活质量，同时病情控制需要长期药物维持，给患者造成较大的经济负担[1-2]。因此，寻求一种廉价有效的药物用于UC治疗具有重要意义及经济学价值。肠道屏障功能破坏是UC的特征性改变[3]。我们近期研究发现临床用于2型糖尿病治疗的一线药物二甲双胍能够减轻硫酸葡聚糖（DSS）诱导小鼠UC模型结肠炎的发生，保护肠黏膜上皮屏障功能[4]。……