血管紧张素(1～7)类似物AVE0991抑制血管紧张素Ⅱ诱导心肌肥大  

The Inhibitory Actions of Angiotensin(1-7) Analogue AVE0991 on Myocardial Cellular Hypertrophy Induced by Angiotensin Ⅱ

作　　者：陈胜龙[1] 何建桂[1] 黄艺仪[1] 陈艺莉[1] 董吁钢[1] 

机构地区：[1]广州中山大学附属第一医院心内科,广东广州510080

出　　处：《中华高血压杂志》2009年第8期706-710,共5页Chinese Journal of Hypertension

基　　金：广东省自然科学基金(No.5001675)FAX:[phone]

摘　　要：目的探讨新合成的血管紧张素(1～7)[Ang(1～7)]类似物AVE0991对血管紧张素Ⅱ(AngⅡ)诱导心肌肥大的抑制作用。方法在AngⅡ(10-6mol/L)诱导培养的SD乳鼠心肌细胞中,应用AVE0991及Ang(1～7)受体拮抗剂A-779等干预细胞,通过测定心肌细胞蛋白质合成速率,蛋白质含量和细胞表面积等指标,观察心肌细胞肥大情况;并利用RT-PCR及Western blot测定AVE0991对重要增殖信号通路转化生长因子(TGF)β1/Smad2的影响。结果AVE0991呈剂量依赖性抑制AngⅡ诱导培养的心肌细胞的蛋白质合成速率,并能减少AngⅡ诱导培养的心肌细胞的蛋白质含量和表面积;AVE0991通过明显下调AngⅡ诱导TGFβ1/Smad2信号通路的表达。但AVE0991的以上效应可被Ang(1～7)受体拮抗剂A-779完全抑制。结论非肽类化合物AVE0991能抑制AngⅡ诱导的心肌细胞肥大,这一生物学效应可能与其抑制TGFβ1/Smad2信号通路有关。Objective To investigate the inhibitory actions of angiotensin（1--7） analogue AVE0991 on myocardial cellular hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ）. Methods The effect of myocardial hypertrophy was observed after treatment with Ang Ⅱ （10-6 mol/L） with or without the presence of AVE0991. The antagonism effect of A-779, an Ang（1--7） receptor antagonist, co-cultured with AVE0991 were also studied in myocardial cells obtained from neonatal SD rats. The protein synthetic rate, protein amounts and surface area of myocardial cells were determined, and the expressions of transforming growth factor （TGF）β1 and Stood2 were assessed by RT-PCR and Western blot. Results AVE0991 inhibited synthetic rate of myocardial cells induced by Ang Ⅱ in a dose-dependent manner. AVE0991 also reduced protein contents and surface area of myocardial cells induced by Ang Ⅱ. AVE0991 significantly inhibited the expressions of TGFβ1/Stood2 induced by Ang Ⅱ. The aboved-mentioned effects of AVE0991 were abolished by Ang（ 1-7） receptor antagonist A-779. Conclusion The nonpeptide Ang（ 1--7 ） receptor agonist AVE0991 attenuates myocardial hypertrophy induced by Ang Ⅱ via down-regulation of TGF-β1/Smad2 expressions.

关 键 词：AVE0991 血管紧张素(1~7) 血管紧张素Ⅱ 心肌肥大 转化生长因子β1/Smad2 

分 类 号：R96[医药卫生—药理学]