高脂饮食性非酒精性脂肪性肝病大鼠肝脏PPAR-γ表达增强  

Overexpression of peroxisome proliferator-activated receptor gamma in liver of rats with non-alcoholic fatty liver disease chronically fed with high-fat diet

作　　者：范建高[1] 丁晓东[2] 王国良[1] 徐正婕[1] 田丽艳[1] 郑晓英[1] 

机构地区：[1]上海交通大学附属第一人民医院消化内科/脂肪肝诊治中心,200080 [2]上海第二医科大学附属新华医院消化内科

出　　处：《肝脏》2004年第4期225-228,共4页Chinese Hepatology

基　　金：上海市青年科技启明星及其跟踪计划

摘　　要：目的　探讨过氧化物酶体增值物活化受体γ(PPAR-γ)及其亚型在高脂饮食所致非酒精性脂肪性肝病(NAFLD)大鼠肝脏的表达及其意义。方法　模型组SD大鼠给予高脂肪高胆固醇饮食饲养 ,分批于实验第 8、12、2 6、2 4周处死 ,同期设普通饮食饲养大鼠作对照。免疫组织化学和RT-PCR分别检测大鼠肝脏PPAR-γ的表达。结果　模型组大鼠第 8周呈现单纯性脂肪肝 ,第 12～ 2 4周从脂肪性肝炎进展为脂肪性肝炎伴肝纤维化。免疫组织化学和RT PCR显示 ,随着造模时间延长 ,肝脏PPAR-γ的表达逐渐增强。模型组肝脏PPAR-γ1mRNA表达于第 2 4周达到高峰 (与对照组相比升高 3 .5倍 ,P <0 .0 1) ,PPAR-γ2 mRNA表达于造模第 16周时达高峰 (较对照组升高 5 .8倍 ,P <0 .0 1)。相关分析显示 ,仅PPAR-γ2 mRNA与肝脂变程度之间关系密切 (r =0 .89,P <0 .0 5 )。结论　持续 2 4周的高脂饮食可以成功复制大鼠NAFLD模型 ,模型大鼠肝脏PPAR-γ表达增强 ,NAFLD大鼠肝细胞可能部分具有脂肪细胞的特征 。Objective To investigate the expression and possible roles of peroxisome proliferator-activated receptors gamma (PPAR-γ) subtypes of γ_1,γ_2 in liver of rats with nonalconholic fatty liver disease(NAFLD) chronically fed with a fat-rich diet. Methods For inducing NAFLD model, a fat-rich diet consisted of 10% lard oil+2% cholesterol was given to Sprague-Dawley rats for a period of 8, 12, 16 and 24 wk, respectively. The other rats fed with normal diet were taken as normal control. Expression of PPAR-γ in the liver were detected by immunohistochemistry and semi-quantitative RT-PCR.Results Simple fatty liver were observed in model grouup at 8wk. From 12wk to 24wk, the liver gradually progressed from steatohepatitis alone to steatohepatitis with fibrosis. Both immunohistochemistry and semi-quantitive RT-PCR suggested the up-regulated expression of PPAR gamma with time in the liver of rats with NAFLD. Expression of PPAR-γ_1 mRNA were peaked in 24wk by 3.5 folds compared to control group(P<0.01), PPAR-γ_2 mRNA peaked in 16wk by 5.8 folds (P<0.01). A positive correlation was only founded between the expression of PPAR-γ_2 mRNA and the severity of liver steatosis(r=0.89,P<(0.05)).Conclusion The rat model for NAFLD can be established sucessfully by feeding with fat-rich diet for 24wk.PPAR-γ_1 and γ_2 were expressed un-regulated in liver of NAFLD, and these changes might stimulate the fatty liver differentiate to have some characteristics of adipocyte which named“adipogenic hepatic steatosis or hepatic adiposis”.

关 键 词：PPAR-Γ 大鼠 肝脏 鼠肝 表达 高脂饮食 NAFLD 非酒精性脂肪性肝病 对照组 造模 

分 类 号：R575[医药卫生—消化系统] R734.2[医药卫生—内科学]