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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 effect of AVE0991, an angiotensin (1 ~ 7) angiotensin (Ang7-7) analogue, on cardiac hypertrophy induced by angiotensin Ⅱ (Ang Ⅱ). Methods AVE0991 and Ang-1 receptor antagonist A-779 were used in cultured neonatal rat cardiomyocytes induced by AngⅡ (10-6 mol / L). The protein synthesis rate, protein content And cell surface area were measured to observe the cardiomyocyte hypertrophy. The effects of AVE0991 on the expression of TGFβ1 / Smad2 were determined by RT-PCR and Western blot. Results AVE0991 inhibited the protein synthesis rate of AngⅡ-induced cardiomyocytes and the protein content and surface area of AngⅡ-induced cardiomyocytes in a dose-dependent manner. AVE0991 down-regulated AngⅡ-induced TGFβ1 / Smad2 signaling pathway. However, the above effect of AVE0991 can be completely inhibited by Ang (1-7) receptor antagonist A-779. Conclusion Non-peptide AVE0991 can inhibit Ang Ⅱ-induced cardiomyocyte hypertrophy, which may be related to its inhibition of TGFβ1 / Smad2 signaling pathway.