血管紧张素Ⅱ灌注在脂质肝损伤中的作用研究  

The role of angiotensinⅡ perfusion in fatty liver injury

作　　者：吴娱[1] 张洋[1] 胡泽波[1] 刘亮[1] 王桂花[1] 鲁荐 马坤岭[1] 

机构地区：[1]东南大学附属中大医院肾内科,江苏南京210009

出　　处：《东南大学学报（医学版）》2015年第5期740-744,共5页Journal of Southeast University(Medical Science Edition)

基　　金：国家自然科学基金资助项目(81470957;81170792);江苏省自然科学基金资助项目(BK20141343)

摘　　要：目的:通过制备血管紧张素Ⅱ(AngⅡ)灌注模型,观察AngⅡ在脂质肝损伤中的作用及其可能的机制。方法:将C57BL/6小鼠随机分为对照组、AngⅡ灌注组及AngⅡ灌注加AngⅡ1型受体(AT1R)基因敲除组。采用HE、菲律宾、油红0染色以及胞内胆固醇定量测定法观察肝细胞内脂质沉积情况;免疫组化、蛋白质印迹法检测低密度脂蛋白受体(LDLR)、固醇调节元件结合蛋白2(SREBP-2)及其裂解激活蛋白(SCAP)表达水平。结果:AngⅡ刺激增加C57BL/6小鼠肝细胞内脂质沉积,且上调LDLR、SREBP-2和SCAP的表达。而AT1R基因敲除组C57BL/6小鼠肝细胞内脂质沉积明显减少,LDLR通路的相关蛋白表达也显著下调。结论:AngⅡ通过AT1R诱导LDLR负反馈调节失调,进而增加胆固醇内流、肝细胞内脂质过度沉积,介导脂质肝损伤的发生。Objective：To investigate the possible effects of angiotensinⅡ（ AngⅡ） on fatty liver injury and its possible mechanism via the construction of AngⅡ perfusion model.Methods： C57BL/6 mice were randomly divided into three groups：the control group, the AngⅡ group and the AngⅡ with angiotensinⅡ type 1 receptor （AT1R） gene knockout group.Lipid accumulation was examined with haematoxylin-eosin（HE） staining, Oil red O staining, Filipin staining, and a quantitative assay of intracellular cholesterol.The protein expressions of low-density lipoprotein receptor （ LDLR ） , sterol regulatory element-binding protein 2 （ SREBP-2 ） and its cleavage activating protein （ SCAP） were determined by immunochemical staining and Western blotting.Results： AngⅡstimulation increased lipid deposition in livers of C57BL/6 mice, which was associated with increased protein expression of LDLR,SCAP, and SREBP-2.However, lipid accumulation in hepatic cells of AT1R gene knockout C57BL/6 mice dropped; moreover, the expression of LDLR pathway related protein significantly dropped. Conclusion：AngⅡdisrupts LDLR feed-back regulation via its receptor AT1R to increase cholesterol uptake and induce intracellular lipid accumulation, contributing to the development of liver injury.

关 键 词：血管紧张素Ⅱ灌注 低密度脂蛋白受体 脂质肝损伤 

分 类 号：R575.5[医药卫生—消化系统]