吡格列酮对SD大鼠非酒精性脂肪肝病形成的预防作用及其机制  

Preventive effect of pioglitazone against nonalcoholic fatty liver disease in Sprague-Dawley rats and its mechanism

作　　者：张佳妮[1] 陈金虎[1] 谭莺[1] 刘慧霞[1] 

机构地区：[1]中南大学湘雅医院老年病科,湖南省长沙市410078

出　　处：《世界华人消化杂志》2009年第8期758-764,共7页World Chinese Journal of Digestology

摘　　要：目的:探讨吡格列酮(pioglitazone,PIO)对SD大鼠非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)形成的干预作用及机制.方法:♂SD大鼠72只,随机分为正常饮食组(NG)、高脂饮食组(HG)和PIO干预组(PIOG)各24只.PIOG喂饲高脂饲料,并同时予PIO药物灌胃8wk.正糖高胰岛素钳夹实验检测IR水平,放免法和全自动生化仪检测血清生化指标,RT-PCR检测过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptorγ,PPARγ)mRNA表达,Western blot检测肝组织c-Jun氨基末端激酶(c-Jun amino-terminal kinase1,JNK1)和PPARγ蛋白表达.结果:HG大鼠GIR水平降低和JNK1蛋白表达增高,均呈明显时间依赖性(均P<0.05);8wk末HG大鼠肝细胞出现明显脂肪变性,与NG相比,体质量、肝指数,TG、ALT、AST、FFAs、FINS、TNF-α水平明显增高,IR加重,JNK1蛋白表达明显升高,肝组织PPARγ表达明显降低(TG:1.23±0.08vs0.62±0.12,ALT:92.80±7.09vs51.34±8.12;AST:153.22±20.65vs119.26±13.61;FFAs:511.94±24.88vs335.31±15.71;FINS:41.23±1.84vs22.65±2.25;TNF-α:1.02±0.12vs0.34±0.07,均P<0.05);而PIOG大鼠,上述各项指标均得到明显改善,但仍不能完全达到NG大鼠水平(均P<0.05).结论:PIO对于由高脂饮食诱导的NAFLD的形成及其他IR相关疾病有预防作用.AIM： To explore the prevention effect and mechanism of pioglitazone （PIO） on nonalcoholic fatty liver disease （NAFLD） in rats. METHODS： Seventy two Sprague-Dawley rats were randomly divided into three groups： normal diet group （NG）, high fat diet group （HG） and PIO group （PIOG）, with 24 rats in every group. PIOG were fed with high fat diet and PIO for eight weeks. IR was tested by euglycemic- hyperinsulinemic clamp; TG, ALT, AST, FFAs, FINS and TNF-α were tested by biochemistry automatic analyzer or RIA; mRNA expression of peroxisome proliferator-activated receptor （PPARγ） was detected using RT-PCR. The expression of PPARγand c-Jun amino-terminal kinase 1 （JNK1） were detected by Western blot.RESULTS： The glucose infusion rate （GIR） decreased and JNK1 increased in HG rats in a time-dependent manner from Ist to 8th week （P 〈 0.05）. Compared with NG, at the end of 8th week, the hepatic steatosis was significant in HG group. The weight, liver index, serum levels of TG, ALT, AST, FFAs, FINS and TNF-α increased, while IR was aggravated. Meanwhile, the JNK1 protein expression in liver tissue was up-regulated, while expression of PPARγ was decreased （TG： 1.23 ± 0.08 vs 0.62 ± 0.12; ALT： 92.80±7.09 vs 51.34±8.12; AST： 153.22 ± 20.65 vs 119.26±13.61; FFAs： 511.94 ± 24.88 vs 335.31 ± 15.71; FINS： 41.23±1.84 vs 22.65 ± 2.25; TNF-α;1.02 ± 0.12 vs 0.34 ±0.07, all P 〈 0.05）. In PIOG, all the indexes were improved, but didn＇t completely return to the same as those of NG group. CONCLUSION： PIO could prevent NAFLD induced by a high-fat diet and other IR-related diseases.

关 键 词：C-JUN氨基末端激酶 非酒精性脂肪肝病 胰岛素抵抗 吡格列酮 

分 类 号：R575[医药卫生—消化系统]