阿托伐他汀对急性心肌梗死后1周兔心室肌细胞L-钙离子通道电流的影响

Effects of Atorvastatin on L-type Calcium Current in Ventricular Myocytes from Infarcted Heart of Normocholesterolemic Rabbits

目的通过研究阿托伐他汀预处理对兔急性心肌梗死后1周心室肌细胞L-钙离子通道电流(ICa-L)的影响,探讨他汀类药物抗心律失常的细胞学离子机制。方法 60只新西兰大耳白兔随机分为3组:心梗组、阿托伐他汀治疗组和假手术对照组。采用结扎兔冠状动脉左前降支的方法建立急性心肌梗死动物模型,采用酶解的方法分离心室肌外膜单个心室肌细胞,采用全细胞膜片钳技术,记录跨膜ICa-L,同时检测各组血脂水平。结果各组动物血脂水平无显著性差异。1周后对照组、心梗组和他汀组ICa-L电流密度峰值(0mV)分别为(-4.21±1.12)pA/pF(n=20),(-3.36±0.92)pA/pF(n=20)和(-4.05±0.56)pA/pF(n=20)。心梗组较对照组明显下降(P<0.05),他汀组较心梗组明显升高(P<0.05)。另外,心梗组ICa-L失活曲线较对照组左移,他汀组较心梗组右移。结论急性心肌梗死可导致梗死区心肌细胞ICa-L明显下降,阿托伐他汀预处理可减轻ICa-L的异常变化,逆转电重构,而不依赖于降血脂效应,可能为他汀类药物降低心律失常发生率的细胞学离子机制。

Objective To investigate the effects of atorvastatin on membrane L-type calcium current（I Ca-L） in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction（AMI）,so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Metheds Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral atorvastatin 5mg/（kg.d）（statin group） or placebo（AMI group） for 7 days. 1 week later,single ventricular myocytes were isolated enzymatieally from the epicardial zone of the infracted region. Whole cell patch clamp technique was used to record ICa-L. Results There was not significant difference in serum cholesterol concentration among three groups. The peak I Ca-L current density （at 0 mV） was significantly decreased in AMI group（-3.36 ±0.92）pA/pF（n=20） compared with CON（-4.21 ± 1.12）pA/pF（u=20）,P〈0.05,while it was significantly increased in statin group （-4.05 ±0.56）pA/pF（u=20） compared with AMI group,P〈0.05. The steady-state inactivation curve was shifted significantly in the hyperpolarizing direction in AMI group compared with CON,while it was shifted in the right direction in statin group compared with AMI group. Conclusion It is indicated that AMI induces significant reduction in ICa-L. The ICa-L down-regulation may underlie the altered electrical activity of the surviving ventricular myocytes. Pretreatment with atorvastatin could attenuate this change without lowering the serum cholesterol level,suggesting that atorvastatin could reverse this electrical remodeling,thus contributing to the ionic mechanism of statin treatment for antiarrhythmia.