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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(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第4期
页码:
453-456,466
栏目:
基础研究
出版日期:
2009-06-25

文章信息/Info

Title:
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
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
Author(s):
DING Chao1 HE Zhen-shan1 CHEN Hui-xiao1 Yang Li1 CHENG Bao-qing2 HUA Li3
1.Department of Cardiology, PLA Bethune International Peace Hospital, Shijiazhuang 050082, Hebei, China; 2.Department of Internal Medicine, PLA 518th Hospital, Xian 710043, Shaanxi, China; 3.Department of Internal Medicine, General Hospital of Jilin Provincial Corps, Chinese Peoples Armed Police Forces, Changchun 130052, Jilin, China
关键词:
辛伐他汀心肌梗死膜片钳离子通道
Keywords:
simvastatin myocardial infarction sodium channels patch-clamp myocardium rabbit
分类号:
R972.6;R541.7
DOI:
-
文献标识码:
A
摘要:
目的 研究辛伐他汀预处理对兔急性心肌梗死(AMI)后24 h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3 d给予辛伐他汀 5 mg/(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(-30 mV)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。
Abstract:
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, AMI group 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.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期:2008-1-31.通讯作者:丁超,副主任医师,博士,主要从事心脏介入及电生理学研究Email:dingch2001@sohu.com
更新日期/Last Update: 2009-06-15