血管紧张素转化酶2基因转染对实验性动脉硬化兔斑块炎症的影响  

Overexpression of angiotensin converting enzyme 2 inhibits inflammatory response of atherosclerotic plaques in hypercholesterolemic rabbits

作　　者：董波[1] 张月辉[2] 董秋立[2] 于庆涛[2] 朱莉[2] 李树英[2] 杨亚培[2] 张澄[2] 冯进波[2] 刘春喜[2] 宋怀东[3] 潘春明[3] 张运[2] 

机构地区：[1]山东大学附属山东省立医院心内科,济南250021 [2]山东大学齐鲁医院国家卫生部教育部心血管重构与功能研究重点实验室 [3]上海交通大学医学院附属瑞金医院 国家南方基因中心

出　　处：《中华心血管病杂志》2009年第7期622-625,共4页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30470701）;山东省科委基金资助项目（Y2006C68,03BS037）

摘　　要：目的探讨血管紧张素转化酶2（ACE2）基因转染是否能通过使血管紧张素（Ang）Ⅱ转化为Ang1-7而抑制动脉硬化斑块的炎症反应。方法克隆小鼠ACE2基因，并构建复制缺陷重组腺病毒质粒Ad-ACE2；用球囊损伤内皮细胞及高脂饲养建立兔动脉硬化模型，喂养3个月，将38只新西兰大白兔随机分为Ad—ACE2及Ad—EGFP两组，每组19只。Ad—ACE2组注射ACE2的腺病毒（2．5×10^9pfu／ml）入兔的腹主动脉中，Ad-EGFP组注射Ad—EGFP，注射1个月后处死动物，取腹主动脉，检测巨噬细胞和单核细胞趋化因子（MCP-1）蛋白的表达；同时应用实时定量PCR检测MCP-1基因的表达。结果Ad—ACE2组的动脉硬化斑块中的巨噬细胞阳性表达率（13．6％±4．2％）明显低于Ad-EGFP组（23．6％±6．9％，P〈0．01）；而基因转染后MCP-1蛋白的表达（13．2％±0．4％）明显低于Ad—EGFP组（25．0％±7．4％，P〈0．01）。结论ACE2基因转染抑制了MCP-1的蛋白表达及巨噬细胞浸润程度，提示ACE2基因具有抑制动脉粥样硬化斑块炎症的作用。Objective Angiotensin converting enzyme 2 （ACE2） efficiently hydrolyses the potent vasoconstrictor angiotensin Ⅱ to vasodilative angiotensin （1-7）. We hypothesized that ACE2 overexpression may inhibit inflammation response in atherosclerotic plaque by degrading Ang Ⅱ into Ang-（1-7）. Methods Atherosclerosis （AS） plaques were induced in the abdominal aorta of 38 rabbits by endothelial injury and atherogenic diet for 3 months. Rabbits were then underwent injection of a recombinant adenovirus （2.5 × 10^9 pfu/ml） carrying a murine ACE2 gene （Ad-ACE2） through a catheter into the abdominal aortic segments rich in plaques （n = 19） or injection of a control vector Ad-EGFP （n = 19 ）. One month later, all rabbits were sacrificed and plaques from aortic segments were analyzed. Results ACE2 expression in aortic tissues of the Ad-ACE2 group were confirmed by immunohistochemistry. Mcrophage infiltration （13.6% ± 4.2% vs. 23.6% ±6.9% , P〈0.01） and MCP-1 expression （13.2% ±0.4% vs. 25.0% ±7.4% , P〈0.01） were significantly reduced in Ad-ACE2 group compared to Ad-EGFP group. Conclusions Overexpression of ACE2 inhibited atherosclerotie plaque inflammation response in hypercholesterolemie rabbits.

关 键 词：动脉硬化 肽基二肽酶A 基因 转染 

分 类 号：R686[医药卫生—骨科学]