二甲双胍对实验性大鼠脂肪肝的治疗作用

Therapeutic effects of metformin on rats with fatty liver

目的:观察二甲双胍治疗脂肪肝大鼠在生化、病理、脂肪代谢、胰岛素及瘦素各方面指标的变化.方法:雄性Wistar大鼠32只,按体重层次随机分为3组,对照组(A)10只、模型组(B)11只、二甲双胍组(C)11只,对照组饲以普通鼠饲料,其余两组均饲以高脂饲料.饲养8wk后病理证实脂肪肝已形成.随后进行灌胃治疗,C组170mg/(kg·d)每天1次5mL灌胃,A组及B组大鼠灌服等量蒸馏水,各组按原饲料进行饲养.8wk后,全部处死,取血及肝组织,测定血中ALT、AST、TG、CHO、INS、FBS、FFA、Leptin.肝组织匀浆测定肝组织TC,TG,SOD、MDA.观察肝脏组织学变化.结果:脂肪肝大鼠存在明显脂肪代谢紊乱,肝功能异常,胰岛素抵抗及leptin表达增高;二甲双胍能显著改善肝功能,ALT(1184.40±244.38vs819.83±143.86nkat/L,P<0.05),AST(3802.76±1532.81vs2959.26±540.44nkat/L,P<0.05)、降低血甘油三酯(2.28±0.50vs1.17±0.36mmol/L,P<0.05),降低leptin高表达(2.47±0.21vs2.19±0.20μg/L,P<0.05)、改善胰岛素抵抗(15.20±7.96vs13.10±5.22,P<0.05),并改善肝组织学.结论:二甲双胍对实验性大鼠脂肪肝有一定治疗效果.

AIM: To investigate the changes of the liver function, histology, fatty metabolism and contents of insulin and leptin after treated with metformin in rats with fatty liver. METHODS: Thirty-two male Wistar rats were randomly devided into three groups: control group (n = 10), model group (n= 11) and metformin group (n= 11). During the whole experiment, the rats in control group were fed with normal food, and the rats in the other two groups were fed with a high caloric laboratory chow. Then the rats in the metformin group were given metformin 170 mg/(kg·qd) while the ones in the other groups were given distilled water of the same volume by stomach irrigation for eight weeks. Then a11 the animals were sacrificed. Liver index (1 iver/body weight ratio), Activities of serum liver-associated enzymes, blood lipids, free fatty acids (FFA), leptin, fasting blood glucose (FBG), fasting plasma insulin (FPI), HOMA insulin resistance index (HOMA-IR), liver triglycerides, liver cholesterol, liver tissue malondialdehyde (MDA), super-oxide dismutase (SOD) and the liver histology of rats in all the groups were detected and analyzed. RESULTS: Significant insulin resistance, disorder of fatty metabolism and liver function and increased expression of leptin were detected in rats of model group. FBG and FPI showed an increasing tendency, but there was no significant difference among the three groups. The liver histology in the model group showed moderate to severe steatosis. After treated with metformin, the levels of serum ALT (1 184.40±244.38 vs 819.83±143.86 nkat/L, P<0.05), AST (3 802.76±1 532.81 vs 2 959.26±540.44 nkat/L, P<0.05), TG (2.28±0.50 vs 1.17±0.36 mmol/L, P<0.05) were decreased significantly. HOMA-IR (15.20±7.96 vs 13.10±5.22, P<0.05) in the metformin group were significantly lower, and the levels of serum leptin (2.47±0.21 vs 2.19±0.20 μg/L, P<0.05) decreased markedly. The liver histology in the metformin group was improved significantly. CONCLUSION: Metformin is effective in the treatment of rats with fatty liver induced by high fat feeding.