二甲双胍对大鼠高脂饮食性脂肪肝的预防和治疗作用

Study on Preventive and Therapeutic Effects of Metformin on Rat Fatty Livers Induced by High Fat Feeding

目的探讨二甲双胍对大鼠高脂饮食性脂肪肝的预防治疗作用。方法 36只SD大鼠随机分为6组:正常对照1、2组给予标准饲料;脂肪肝模型1、2组给予高脂饮食;预防组和治疗组分别在高脂饮食喂养3周、10周时加用二甲双胍100mg/(kg.d)灌胃7周。相对应的正常对照组和模型组同期给予等容积蒸馏水灌胃。分别在10周、17周后分批处死动物。结果预防组体重、肝指数、血清和肝脏甘油三酯(TC)、HOMA胰岛素抵抗指数(IR)和肝脂变程度均显著低于模型1组(P<0.05),与正常对照1组无显著差异(P>0.05);治疗组体重、肝指数、血清转氨酶、胰岛素、TG、肝脏TG、HOMA-IR和肝脂变程度均明显低于模型2组(P<0.05),但仍与正常对照2组有显著差异(P<0.05)。结论二甲双胍通过降脂和改善胰岛素敏感性,具有预防和治疗大鼠高脂饮食性脂肪肝的作用,但早期预防效果更佳。

Objective To explore the preventive and therapeutic effects of metformin on rat fatty livers induced by high fat feeding.Methods Totally 36 Sprague-Dawley rats were randomly allocated into 6 groups：Normal groups 1 and 2 fed with standard diet;Fatty liver model group 1 and 2 fed with high-fat diet;Preventive group and therapeutic group respectively fed with high-fat diet for 3 or 10 weeks added metformin hydrochloride talbets 100mg/（kg·d） for 7 weeks while the normal groups and model groups were given distilled water of the same volume by stomach feeding at the same time.The rats were respectively sacrificed 10 or 17 weeks later.Results The body weight,liver index,serum triglycerides and liver triglycerides,the degree of hepatic steatosis and HOMA-IR in the preventive metformin group decreased significantly compared with those in model group 1（P〈0.05）,but there were no significant difference of those indexes between the preventive metformin group and the normal diet group 1（P〉0.05）;The body weight,liver index,serum activities of liver-associated enzymes,fasting plasma insulin,serum triglycerides and liver triglycerides,and HOMA-IR and the degree of hepatic steatosis in the therapeutic metformin group were significantly lower than those in model group 2（P〈0.05）,but significantly higher than those in normal diet group 2（P〈0.05）.Conclusion By reducing blood triglycerides and ameliorating insulin sensitivity,metformin had preventive and therapeutic effects on rat fatty livers induced by high fat feeding,preventing much better than treating.