血管紧张素转换酶2基因转染对内皮细胞的保护作用  

Protective Effect of Angiotensin Converting Enzyme 2 Transfection on Vascular Endothelial Cells

作　　者：郝青青[1,2] 张永欢[1,2] 于庆涛[1] 朱莉[1] 陈旭[1] 李树英[1] 张月辉[1,3] 董波[1] 李瑞峰[2] 

机构地区：[1]山东大学附属省立医院心内科,山东省济南市250021 [2]山东大学医学院病理生理学教研室 [3]南方医科大学附属深圳宝安医院重症医学科

出　　处：《中国循环杂志》2014年第10期841-845,共5页Chinese Circulation Journal

基　　金：国家自然科学基金资助项目(81170207);国家科技部973计划课题(2013CB530700)

摘　　要：目的:探讨血管紧张素转换酶2(ACE2)基因转染对内皮细胞血凝素样氧化型低密度脂蛋白受体-1(LOX-1)表达的影响及意义。方法:实验包括体外实验与体内实验。体外实验,首先进行人脐静脉内皮细胞(HUVEC)的培养,然后应用蛋白质印迹法检测ACE2转染对血管紧张素II刺激HUVEC产生的LOX-1蛋白表达的影响。体内实验,首先建立载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化模型。然后将20只ApoE-/-小鼠随机分为ACE2组及增强型绿色荧光蛋白组(EGFP组),每组10只。ACE2组经尾静脉注射ACE2的复制缺陷重组腺病毒(Ad-ACE2)(2.5×109 pfu/ml),EGFP组注射等量EGFP的复制缺陷重组腺病毒(Ad-EGFP)。注射一个月后处死动物,做腹主动脉的油红O及LOX-1表达的检测。结果:体内实验与体外实验均证实ACE2基因转染抑制了内皮细胞LOX-1的表达,体内实验中ACE2组斑块内脂质含量明显低于EGFP组水平。结论:ACE2通过抑制LOX-1的表达进而抑制了动脉粥样硬化斑块的进展。Objective： To investigate the inlfuence of angiotensin converting enzyme 2 （ACE2） on lectin-like oxidized low density lipoprotein receptor-1 （LOX-1） protein expression and to explore the protective effect of ACE2 on vascular endothelial cells. Methods： Our work includedin vitro andin vivo studies. For in vitro experiment, the human umbilical vein endothelial cell （HUVEC） were cultured and transfected with replication deficient recombinant adenovirus of ACE2 （Ad-ACE2）, and LOX-1 protein expression stimulated by angiotensin 2 was examined by Western blot analysis. Forin vivo study, atherosclerosis plaques were induced in 20 apolipoprotein E-deifcient （ApoE-/-） mice, and then randomly divided them into 2 groups： ACE2 group, the mice received Ad-ACE2 （2.5×109 pfu/ml） injection through caudal vein, EGFP （enhanced green lfuorescent protein） group, the mice received equal replication deifcient recombinant adenovirus of EGFP （Ad-EGFP） injection through caudal vein.n=10 in each group. The animals were executed after 1 month treatment to collect abdominal aorta. Lipid content in atherosclerosis plaque was evaluated by Oil red O staining and LOX-1 protein expression was examined by immunohistochemistry and Western blot analysis. Results： Bothin vitro andin vivo experiments conifrmed that endothelial cell LOX-1 protein expression was signiifcantly inhibited by ACE2 transfection. The lipid content in ACE2 group was obviously lower than that in EGFP group byin vivo study. Conclusion： ACE2 may inhibit LOX-1 protein expression and therefore reduce the progress of atherosclerosis.

关 键 词：动脉粥样硬化 血管紧张素转换酶2 血凝素样氧化型低密度脂蛋白受体-1 基因 

分 类 号：R54[医药卫生—心血管疾病]