摘要
目的:研究碳水化合物反应元件结合蛋白转录因子(carbohydrate responsive element binding protein,ChREBP)及其靶基因含patatin样磷脂酶域3(patatin-like phospholipase domain containing family member A3,PNPLA3)在非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)中的作用以及NAFLD的发病机制.方法:将48只200 g±20 g体质量的成年♂SD大鼠,随机分为对照组24只(普通饲料喂养)和模型组24只(高脂饲料喂养),分别于第4周末,第8周末和第12周末处死各组大鼠8只,并进行血清生化的测定;在光镜下观察肝组织病理变化;用免疫组织化学方法检测ChREBP蛋白的表达水平;用RT-PCR技术检测肝脏ChREBP以及PNPLA3基因的mRNA的表达.结果:(1)成功构建NAFLD大鼠模型,光镜下观察可见对照组大鼠肝脏组织结构正常,各项生化指标均在正常范围,肝组织内表达少量ChREBP蛋白;(2)模型组大鼠较肥胖,肝脏明显增大,肝细胞内可见脂滴沉积,血清生化天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)水平升高(P<0.05),空腹血糖(fasting blood glucose,FBG)及空腹血胰岛素(fasting serum insulin,FINS)水平升高(P<0.05),并随着喂养时间的增加而逐渐增加(P<0.05),而胰岛素敏感指数(insulin sensitive index,ISI)明显下降(P<0.05);(3)模型组大鼠肝组织ChREBP蛋白和ChREBP、PNPLA3 mRNA的表达水平升高,与对照组差异具有统计学意义(P<0.05),且随造模时间的延长其表达量也增加(P<0.05);(4)相关分析显示,在模型组中,ChREBP mRNA的相对表达量与PNPLA3、血清AST、ALT水平、肝脏炎症活动度计分呈正相关(r=0.409,P<0.05;r=0.498,P<0.05;r=0.677,P<0.01;r=0.729,P<0.01;r=0.566,P<0.01),与ISI呈负相关(r=-0.611,P<0.01).结论:高脂饮食引起ChREBP的表达增强,其可能激活了脂质合成相关基因PNPLA3的表达,并可能通过参与胰岛素抵抗的�
AIM： To explore the role of carbohydrate respon-sive element binding protein（ChREBP） and its target gene patatin-like phospholipase domain containing family member A3（PNPLA3） in the pathogenesis of nonalcoholic fatty liver disease（NAFLD）.METHODS： Forty-eight adult male rats were randomly and equally divided into two groups to receive a normal fed diet（control group） or a high-fat diet（NAFLD model group）. At the end of the 4th, 8th and 12 th week, 8 rats in each group were killed to determine serum biochemical parameters, observe pathological changes in he-patic tissue under a light microscope, detect the expression of ChREBP protein by immunohisto-chemistry, and detect the expression of ChREBP and PNPLA3 mRNAs in the liver by RT-PCR.RESULTS： NAFLD was successfully induced in rats after feeding a high-fat diet. In the control group, rat liver lobule structure was intact under a light microscope, the biochemical parameters were in the normal ranges, and expression of ChREBP protein was weak in the liver tissue. Compared with the control group, rat weight was increased, the volume of the liver was obvi-ously increased, fat drop deposition was visible in liver cells, and the levels of aspartate ami-notransferase（AST）, alanine aminotransferase（ALT）, total cholesterol（TC）, triglycerides（TG）, fasting blood glucose（FBG）, and fasting serum insulin（FINS） were significantly elevated in the model group（P〈0.05 for all）. With the prolon-gation of feeding time, blood AST, ALT, TC, TG FBG and FINS levels were gradually elevated and ISI significantly declined（P〈0.05）. ChREBP protein expression and ChREBP and PNPLA3 mRNA expression in rat liver tissue were in-creased in the model group compared with the control group（P〈0.05）. With the prolongation of feeding time, ChREBP protein expression and ChREBP and PNPLA3 mRNA expression were significantly increased（P〈0.05）. ChREBP mRNA expression in the model group was positively correlated with PNPLA3 expression, ser
出处
《世界华人消化杂志》
CAS
北大核心
2014年第19期2679-2685,共7页
World Chinese Journal of Digestology
