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

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(Ans)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(2.5×109pfu/m1)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.

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

Objective Angiotensin converting enzyme 2 (ACE2.) efficiently hydroiyses 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 × 109 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 atherosclerotic plaque inflammation response in hypercholesterolemic rabbits.