二甲双胍干预大鼠非酒精性脂肪性肝炎疗效观察

Therapeutic effects of metformin on rats with nonalcoholic steatohepatitis

目的观察二甲双胍对非酒精性脂肪性肝炎大鼠模型的干预作用。方法实验动物分3组,模型组和治疗组各12只雄性SD大鼠给予高脂肪高胆固醇饲料喂养,另设6只普通饲料喂养大鼠作为对照组。治疗组从高脂饮食第4周起在饮水中加用二甲双胍(每天250mgkg)。所有大鼠均于实验24周后处死,进行血清生化和肝脏组织学检测。结果与模型组相比,治疗组肝脏指数和腹腔脂肪含量显著减少(P均<0.001),且体重呈下降趋势;血清天冬氨酸转氨酶[(162.45±11.2)UL比(115.9±29.3)UL,P=0.01]、三酰甘油(1.10±0.24比0.75±0.30,P=0.01)水平显著下降;治疗组肝脏组织学炎症评分(1.20±1.14比4.83±1.05,P<0.01)和肝纤维化评分(0.70±0.48比1.42±0.45,P<0.05)显著下降,伴肝脂肪变程度减轻(P<0.05)。结论二甲双胍早期干预可显著改善高脂饮食大鼠脂肪性肝炎和纤维化程度,伴肝重、腹部脂肪含量及血清三酰甘油水平下降。

Objective To investigate the therapeutic effects of metformin on rat with nonalcoholic steatohepatitis (NASH).Methods Tirty male SD rats were divided into 3 groups,the NASH group(n=12) and metformin group(n=12) both were fed with a fat-rich diet,and the control group(n=6) with normal diet.From 4wk,metformin(250 mg·kg -1 ·d -1 ) was given to the rats with water. All rats were sacrificed at week 24.Results Metformin reduced liver index and abdominal viscera fat index induced by fat-rich diet.Biochemistry analysis revealed that compared with controls metformin reduced AST(115.9±29.3 vs 162.4±11.2,P=0.0007),triglyceride(TG) (0.75±0.30 vs 1.10±0.24,P=0.012), and free fatty acid (0.450±0.167 vs 0.626 ±0.201,P=0.061).Pathologically,metformin lighten the liver steatosis,hepatic histologic activity scores of inflammation (HAI) (1.20±1.14 vs 4.83± 1.05 ,P<0.01) and scocres of fibrosis(0.70±0.48 vs 1.42±0.45,P<0.05).Conclusion Metformin could improve biochemical parameters of hepatic injury,lightening liver steatosis,reducing serum TG,HAI scores and fibrosis.This study provides evidence that using metformin to treat NASH is worth further investigation.