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血管紧张素Ⅱ灌注在脂质肝损伤中的作用研究
作者:吴娱  张洋  胡泽波  刘亮  王桂花  鲁荐  马坤岭 
单位:东南大学附属中大医院 肾内科, 江苏 南京 210009
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
出版年·卷·期(页码):2015·34·第五期(740-744)
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AngⅡ 1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: AngⅡ stimulation 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: AngⅡ disrupts LDLR feed-back regulation via its receptor AT1R to increase cholesterol uptake and induce intracellular lipid accumulation, contributing to the development of liver injury.

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