二甲双胍对高脂饲养大鼠肝脏脂肪变的干预作用  

Effects of metformin on hepatic steatosis induced in rats fed a high fat diet

作　　者：陈世清[1] 黎华[1] 刘杞[2] 

机构地区：[1]郧阳医学院附属太和医院,湖北省十堰市442000 [2]重庆医科大学病毒性肝炎研究所教育部感染性疾病分子生物学重点实验室,重庆市400010

出　　处：《世界华人消化杂志》2007年第16期1810-1814,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨胰岛素抵抗在非酒精性脂肪性肝发病中的作用及机制,观察二甲双胍对高脂饲养大鼠肝脏脂肪变的干预效果.方法:21只(?) Wistar大鼠分为3组,每组7只,普通饮食组(SD),高脂饮食组(HF),二甲双胍组(HF- Met)在高脂饮食的同时给予二甲双胍,共8wk.8 wk末处死大鼠,称量附睾脂肪,计算肝指数,生化方法测定ALT、AST、TG、TC、FFA、SOD和MDA.放免法测定空腹胰岛素,逆转录聚合酶链反应(RT-PCR)和ELISA法检测肝脏TNF-αmRNA和蛋白的表达,用葡萄糖输注率(GIR)来评价胰岛素敏感性,并观察肝组织病理变化.结果:与HF相比,HF-Met肝细胞脂肪变和小叶炎症明显减轻,肝指数、胰岛素、AST、ALT、TG、FFA显著下降(3.25±0.26 vs 4.29±0.12,33.37±8.34 vs 46.73±5.24,17.29±5.34 vs 43.48±6.21,4.10±2.47 vs 12.05±4.05,P<0.01;106.0±31.04 vs 141.37±24.87,48.31±16.11 vs 88.34±21.94,P<0.05)TNF-α的表达也显著下降,GIR增加(7.58±1.05 vs 6.31±1.28,P<0.05).结论:二甲双胍干预能明显改善高脂饲养大鼠的胰岛素抵抗,降低肝脏TG、FFA和TNF-α的表达,减轻肝脏脂肪变的程度,提示胰岛素增敏治疗可能是NAFLD防治的一种积极策略.AIM： To investigate the role and mechanism of insulin resistance in nonalcoholic fatty liver disease （NAFLD）, and to evaluate the intervening effects of metformin （Met） on rats with hepatic steatosis induced by feeding a high fat diet. METHODS： Twenty-one male Wistar rats were randomly divided into three equal groups. Rats in standard chow group （SD） were fed normal food, those in the high fat diet group （I-IF） had a high fat diet, and rats in the HF-Met group were fed a high fat diet but gavaged with Met for 8 weeks. Rats were sacrificed at the end of 8 weeks to weigh epididymal fat and calculate the liver index. Levels of ALT, AST, insulin, TG, TC, FFA, SOD, and MDA were detected by biochemistry, and fasting insulin by radioimmunoassay. mRNA and protein expression of hepatic TNF-α were detected by reverse-transcriptase polymerase chain reaction （RT-PCR） and Enzyme linked immunosorbent assay （ELISA）, respectively. Insulin sensitivity was measured with Glucose Infusion Rate （GIR） by the euglycermic hyperinsulinemia clamp technique. Assessments of steatosis and inflammatory activity in all rats were scored under light microscope. RESULTS： Notable steatosis and lobular inflam- matory activities were more decreased in HF- Met than those in HF. The liver index, insulin, and levels of AST, ALT, TG and FFA were sig- nificantly decreased in HF-Met compared with those in HF （3.25±0.26 vs 4.29 ± 0.12, 33.37 ± 8.34 vs 46.73 ± 5.24, 17.29 ± 5.34 vs 43.48 ± 6.21, 4.10 ± 2.47 vs 12.05 ± 4.05, P 〈 0.01; 106.0 ± 31.04 vs 141.37±24.87, 48.31±16.11 vs 88.34±21.94, P 〈 0.05） TNF-α expression also decreased, while GIR increased （7.58 ± 1.05 vs 6.31 ± 1.28, P 〈 0.05）. CONCLUSION： Metformin intervention can markedly improve insulin resistance induced by a high fat diet, decrease the levels of hepatic TG, FFA and TNF-α expression, while lessen hepatic steatosis, suggesting that it could be an active strategy to enhance insulin sensitivity in NAFLD.

关 键 词：非酒精性脂肪性肝病 胰岛素抗药性 二甲 双胍 聚合酶链式反应 酶联免疫测定 

分 类 号：R575.5[医药卫生—消化系统]