血管紧张素Ⅱ诱导下肥大心肌电生理特征和钙调神经磷酸酶活性的改变

Changes of electrophysiological characteristics and calcineurin activity of hypertrophic myocytes induced by angiotensin Ⅱ

目的:探讨血管紧张素Ⅱ(AngⅡ)诱导心肌肥大过程中心肌细胞电生理特性和钙调神经磷酸酶(CaN)活性的改变及其意义。方法:体外培养乳兔心室肌细胞,观察10-7mol/LAngⅡ作用48h心肌细胞肥大指标(细胞体积、总蛋白含量及膜电容)、CaN活性、动作电位时程(APD)、瞬时外向钾电流(Ito)密度的变化。结果:AngⅡ作用48h,心室肌细胞体积、总蛋白含量、膜电容较正常对照组分别增加40.36%、40.44%、38.22%(P<0.01);心室肌细胞CaN活性较对照组增加114.7%(P<0.01);心室肌细胞动作电位复极达90%时限(APD90)较对照组延长22.1%(P<0.01);心室肌细胞Ito密度较对照组下调28.6%(P<0.05)。结论:AngⅡ持续刺激可引起心室肌细胞电重构,可能是导致室性心律失常发生的一个重要机制;CaN依赖的信号通路参与AngⅡ诱导的心肌肥大。

Objective：To explore the electrophysiological characteristics and calcineurin activity of the cultured hypertrophic neonatal rabbit ventricular myocytes （NRVC）induced by angiotensinⅡ （Ang 11 ）. Method： NRVC were cultured in vitro. Myocyte hypertrophic parameters （including myocyte volume, total protein content and membrane capacitance）, calcineurin（CaN） activity, action potential duration（APD） and transient outward potassium current （Ito） density were measured 48 h after Ang Ⅱ stimulation. Result：Compared with control group, 48 h after AngⅡstimulation, ventricular myocyte volume, total protein content and membrane capacitance were increased 40, 36%, 40.44% and 38. 22%, respectively（P〈0.01） ; APD at 90% repolarization（APD90） of NRVC was prolonged by 22.1% （P〈0.01） ; Ito density was decreased by 28.6%（P〈0.05）. Conclusion：Chronic Ang Ⅱstimulation could produce the electrophysiological remodeling of ventricular myocytes, which could be an important mechanism of ventricular arrhythmia. CaN-dependent signaling may involve the myocyte hypertrophy induced by Ang Ⅱ.