辛伐他汀对急性心肌梗死兔的心室肌细胞钠离子通道电流的影响  

Effects of simvastatin on sodium ion channel current in ventricular myocytes from rabbits with acute myocardial infarction

作　　者：丁超[1] 何振山[1] 陈会校[1] 杨莉[1] 程保青[2] 花莉[3] 

机构地区：[1]解放军白求恩国际和平医院心内科,河北石家庄050082 [2]解放军西安卫星测控中心518医院内科,陕西西安710043 [3]武警吉林总队医院内科,吉林长春130052

出　　处：《心脏杂志》2009年第4期453-456,466,共5页Chinese Heart Journal

摘　　要：目的研究辛伐他汀预处理对兔急性心肌梗死(AMI)后24h心室肌细胞钠离子通道电流的影响,并探讨他汀类药物抗心律失常的细胞学离子机制。方法采用结扎兔冠状动脉左前降支的方法,建立AMI动物模型。将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[他汀组,手术前3d给予辛伐他汀5mg/(kg.d)]及假手术对照组(只开胸不结扎血管)。采用酶解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,记录跨膜钠离子通道电流(INa),同时应用全自动生化分析仪检测各组血脂的水平。结果各组动物血脂的水平无显著差异。对照组、心梗组和他汀组的INa电流密度峰值(-30mV)分别为(-42.78±5.48)pA/pF(n=16)、(-23.26±5.18)pA/pF(n=12)和(-39.23±5.45)pA/pF(n=13)。心梗组较对照组明显下降(P<0.01),他汀组较心梗组明显升高(P<0.01)。另外,心梗组INa失活曲线左移,失活后恢复时间延长,他汀组这些异常也明显恢复。结论AMI可导致梗死区心肌细胞INa明显下降,辛伐他汀预处理可减轻INa的异常变化,逆转电重构,而不依赖于降血脂的效应,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。AIM： To investigate the effects of simvastatin on membrane sodium ion channel current （INa） in left ventricular myocytes from rabbits suffering from acute myocardial infarction （AMI） in order to explore the cellular （ionic） basis of statin treatment for antiarrhythmia. METHODS： Rabbits were infarcted by ligation of the left anterior descending coronary artery after the administration of oral simvastatin 5 mg/（kg·d） （statin group） or placebo （AMI group） for 3 days. After 24 h, single ventricular myocytes were isolated enzymatically from the epicardial zone of the infarcted region. Whole cell patch clamp technique was used to record INa. RESULTS： No significant difference in serum cholesterol concentration was observed among the three groups. Peak INa current density （at 30 mV） in CON, AMIgroup and statin group was, respectively, （42.78 ± 5.48 ） （ n = 16）, （23.26 ± 5.18 ） （ n = 12）, and （39.23 ±5.45） pA/pF （n = 13） （AMI group vs. CON and statin group, P 〈0. 01 ）. CONCLUSION： Our findings indicate that AMI induces significant reduction in Ina, and INa downregulation may underlie the altered electrical activity of the surviving ventricular myocytes. Pretreatment with simvastatin can attenuate this change without lowering serum cholesterol level, suggesting that simvastatin may reverse this electrical remodeling, which may be part of the ionic mechanism in statin treatment for antiarrhythmia.

关 键 词：辛伐他汀 心肌梗死 膜片钳 离子通道 兔 

分 类 号：R972.6[医药卫生—药品] R541.7[医药卫生—药学]