二甲双胍对胰岛素抵抗大鼠脂肪肝的影响

Effects of metformin on fatty livers in insulin-resistant rats

目的 探讨二甲双胍对胰岛素抵抗大鼠脂肪肝的影响。方法 雄性 Wistar 大鼠31只，随机分 为正常组(n=8)和实验组(n=23)。正常组普通饮食，实验组高脂饮食，8周末从实验组中随机抽取7只证实造 模成功。实验组再分为二甲双胍组(n=8)和模型对照组(n=8)，6周后，胰岛素敏感性用正常血糖高胰岛素钳 夹技术稳态时的葡萄糖输注率来评价；氨基转移酶、甘油三酯(TG)、游离脂肪酸(FFA)等以生物化学 方法测定；胰岛素和肿瘤坏死因子α(TNF α)分别用放射免疫法和酶联免疫吸附法测定；肝细胞脂肪变 性和肝脏的炎症程度在光学显微镜下评估。结果 与模型对照组相比，二甲双胍组大鼠胰岛素抵抗明显改 善，肝指数、附睾脂肪比重、体重明显下降，氨基转移酶、TG、FFA、TNF α明显降低，肝细胞脂肪变性 和肝脏炎症情况有不同程度的改善。结论 二甲双胍能够明显改善高脂饲养诱发脂肪肝大鼠的胰岛素抵抗 和肝脏组织学，它可能成为治疗脂肪肝的新药物。

Objective To investigate the effects of metformin on fatty livers in insulin-resistant rats. Methods Thirty-one male Wistar rats were randomly divided into a normal （n=8） and an experimental group （n=23）. The normal group rats were fed a standard diet, and those of the experimental group with a high-fat diet. After 8 weeks, 7 rats from the experimental group were sacrificed to verify whether the model was established successfully. Then the experimental group was randomly subdivided into two groups： one with metformin treatment （n=8） and one without （n=8）. After 6 weeks, insulin sensitivity was measured with glucose infusion rate （GIR） by euglycermic hyperinsulinemia clamp technique. Aminotransferase, triglyceride （TG） and free fatty acids （FFA） were measured by biochemical methods, insulin by radioimmunoassay and tumor necrosis factor- α （TNF α ） by ELISA. The steatosis changes and inflammation activity of all rat livers were scored histologically. Results Compared with the model group, the insulin resistance, liver index, visceral adiposity and weight loss of the metformin group were dramatically ameliorated. The steatosis and the inflammatory activity in the livers and the level of serum aminotransferase of the metformin group were also significantly decreased. Furthermore, metformin treatment lowered serum TG, liver lipid accumulation and the production of FFA and TNF α. Conclusion Metformin can significantly improved insulin resistance and fatty liver development in rats fed a high-fat diet. It may become a new choice for fatty liver treatment in the future.