二甲双胍对高糖高脂饮食诱导的糖尿病大鼠脂肪肝的干预作用

Effect of metformin on fatty liver induced by high-glucose and high-fat diet in diabetic rat

目的观察高糖、高脂饮食诱导的糖尿病大鼠肝脏病理改变,探讨二甲双胍的干预作用。方法 40只SD大鼠随机分为正常对照(NC)组、糖尿病对照(DM-C)组和DM+二甲双胍干预(DM-M)组。比较各组生化指标、肝重及肝脏指数的改变。HE染色观察大鼠肝脏形态学变化;免疫组化法检测肿瘤坏死因子α(TNF-α)在肝脏的表达。结果高糖、高脂饲养4周后诱导大鼠出现胰岛素抵抗;8周成功建立T2DM大鼠模型。18周末DM-C组大鼠肝脏出现严重脂肪变性,TNF-α在肝脏的蛋白表达水平增加(P<0.01)。经二甲双胍治疗后,DM-M组大鼠肝脏脂肪变性程度明显减轻,TNF-α的蛋白表达水平下降(P<0.05)。结论二甲双胍可降低高糖、高脂饮食诱导的糖尿病大鼠肝脏脂肪含量,降低TNF-α在肝组织的蛋白表达,对治疗2型糖尿病脂肪肝具有一定的作用。

Objective To investigate the effects of metformin on the fatty liver of type 2 diabetic rat model. Methods 40 SD rats were randomly divided into three groups： normal control （NC）, diabetes mellitus （DM-C） and metformin treatment （DM M）. The levels of plasma glucose, serum insulin, tumor necrosis factor-a（TNF-a） and the expression of TNF-a in the liver were measured. Results Compared with NC group, DM group showed the increased lipid profiles and glucose levels after 4 to 8 weeks of high- glucose and high-fat feeding. After 18 weeks,as compared with NC group, the protein expression of TNF- a was significantly higher （174.5.70 ±703.25 vs 169.78±72.87, P〈0.01 ） in DM-C group. After an intervention with metformin, the TG content of the liver and the level of serum TNF-a were significantly decreased （0.0306±0.0570 vs 0.04.00±0.0120; 1.32±0.32 vs 1.71±0.37, P〈0.05, P〈0.05, respectively）, and the protein expression of TNF-a was significantly lower（163.54±395.97 vs 1745.70± 703.25, P〈0. 05）in DM-M group than in DM-C group. Conclusions Metformin has therapeutic effect on fatty liver in type 2 diabetic rat.