辛伐他汀对兔急性心肌梗死后心室肌细胞L钙离子通道电流的影响.DOCVIP

临床医学论文-辛伐他汀对兔急性心肌梗死后心室肌细胞L钙离子通道电流的影响 【摘要】? 目的 通过研究辛伐他汀预处理对兔急性心肌梗死后24 h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 45只新西兰大耳白兔随机分为3组：心梗组、辛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(AMI)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差异。对照组、心梗组和他汀组ICaL电流密度峰值(0 mV)分别为(-4.56±1.01)pA/pF(n=15)，(-3.23±0.91)pA/pF(n=12)和(-4.18±0.95)pA/pF(n=12)。心梗组较对照组明显下降(P0.05)，他汀组较心梗组明显升高(P0.05)。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，辛伐他汀预处理可减轻ICaL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。 【关键词】? 辛伐他汀 肌梗死 膜片钳 L－钙离子通道电流 ??? Effect of Simvastatin on Ltype Calcium Current in Ventricular Myocytes from Infarcted Heart of? Normocholesterolemic Rabbits? DING Chao, LI Junxia ,CHEN Huixiao，et al．Department of Cardiology,Bethune International Peace Hospital of PLA, Shijiazhuang? 050082，China ??? 【Abstract】? Objective? To investigate the effect of simvastatin on membrane Ltype calcium current (ICaL)? in left ventricular myocytes of rabbit heart suffering from acute myocardial infarction(AMI),so as to explore the ionic mechanism of statin for antiarrhythmia. Methods? Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin? 5 mg·kg-1·d-1 (Statin group) or placebo(AMI group ) for 3 days. 24 h later,single ventricular myocytes were enzymatically isolated 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 the three groups.The peak ICaL current density(at 0 mV) was significantly decreased in AMI group (-3.23±0.91 pA/pF,n=12) compared with CON (-4.56±1.01 pA/pF,n=15, P0.05)，while it was significantly increased in Statin group (-4.18±0.95 pA/pF,n=12)compared with AMI group(P0.05).The steadystate inactivation curve shifted significantly in the hyperpolarizing direction in AMI group compared? with CON, while it shifted in the right direction i