脂联素通过腺苷酸活化蛋白激酶抑制血管紧张素Ⅱ诱导的心房肌细胞肥大

Adiponectin protects against angiotensin Ⅱ-induced atrial myocyte hypertrophy through AMP-activa-ted protein kinase

目的 通过研究腺苷酸活化蛋白激酶（AMP-activated protein kinase,AMPK）在脂联素抑制心房肌细胞肥大过程中的作用,探讨脂联素抑制心房结构重构的机制及其途径.方法 将原代培养的SD乳大鼠心房肌细胞分为对照组、血管紧张素Ⅱ（AngⅡ）组、脂联素组和AngⅡ＋脂联素组.分别加入AMPK的激动剂和抑制剂,通过Western-blot检测AMPK的表达水平,通过实时逆转录聚合酶链式反应（Real-time RT PCR）检测各组细胞心房钠尿肽（ANP）的表达水平.用SPSS16.0软件进行统计学分析.结果 与对照组相比,脂联素能够抑制AngⅡ诱导的ANP表达增高（1.25±0.04对0.97±0.02,P＜0.001）,刺激心房肌细胞AMPK磷酸化水平增高（1.43±0.04）倍（P＜0.001）.AICAR能抑制AngⅡ诱导的ANP表达增高（1.20±0.03对1.06±0.12,P＜0.001）,从而模拟脂联素的作用.Compound C抑制AMPK后,脂联素对ANP的抑制作用减弱（0.97±.0.02对1.11±0.01,P＜0.001）.结论 脂联素能够抑制AngⅡ诱导的心房肌细胞肥大；AMPK介导了脂联素的心房肌细胞保护作用.

Objective We aimed to explore the potential effect of adiponectin on the atrial myocyte hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ）,and investigate whether the effect is related to the AMP-activated protein kinase （AMPK）.Methods Primary culture of atrial myocytes was prepared by trypsin-EDTA digestion from atria of neonatal Sprague-Dawley rats and identified by immunocytochemical analysis of α-actin.The atrial myocytes were divided into four groups：the control group,the Ang Ⅱ group,the gAd group and the Ang Ⅱ ＋gAd group.AICAR,the artificial AMPK activator,or Compound C,the AMPK inhibitor was added to the groups,respectively.The atrial myocyte hypertrophy was measured by atrial natriuretic peptide （ANP）gene expression by RT-PCR.The AMPK activity was assessed by Western blotting.Results In atrial myocytes,adiponectin decreased the expression of ANP induced by angiotensin Ⅱ （1.25±0.04 vs 0.97±0.02,P =0.0001）,and promoted AMPK phosphorylation by 1.43±0.04 fold（P〈0.001）.AICAR significantly attenuated the expression of ANP （1.20± 0.03 vs 1.06 ± 0.12,P 〈 0.001）.However,Compound C increased the expression of ANP （0.97±0.02 vs 1.11±0.01,P〈0.001）.Conclusion Adiponectin may protect against angiotensin Ⅱ-induced atrial myocyte hypertrophy through AMPK.