天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (11): 1296-1299.doi: 10.11958/j.issn.0253-9896.2015.11.020

• 实验研究 • 上一篇    下一篇

依折麦布和辛伐他汀对缺血再灌注大鼠心肌细胞瞬时外向钾电流的影响#br#

张坤， 李广平△， 李健， 程立君， 杨万松， 陈延勋#br#   

  1. 天津医科大学第二医院心脏科， 天津心血管病离子与分子机能重点实验室， 天津心脏病学研究所 （邮编300211）
  • 收稿日期:2015-03-16 修回日期:2015-07-09 出版日期:2015-11-15 发布日期:2015-11-15
  • 通讯作者: 李广平 E-mail： tjcardiol@126.com E-mail:doc.zkun@gmail.com
  • 作者简介:张坤 （1985）， 男， 医学硕士， 主要从事冠心病的基础与临床方面研究

Effects of ezetimibe and simvastatin on transient outward potassium current in ischemiareperfused ventricular myocytes in rats

ZHANG Kun,  LI Guangping△,  LI Jian,  CHENG Lijun,  YANG Wansong,  CHEN Yanxun#br#   

  1. Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Tianjin Institute of Cardiology, Tianjin 300211, China
  • Received:2015-03-16 Revised:2015-07-09 Published:2015-11-15 Online:2015-11-15
  • Contact: LI Guangping E-mail： tjcardiol@126.com E-mail:doc.zkun@gmail.com

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摘要： 目的 研究依折麦布和辛伐他汀单独及联合使用对模拟缺血再灌注大鼠心肌细胞瞬时外向钾电流 （Ito） 的影响。方法 将 75 只雄性 SD 大鼠按随机数字表法分为正常对照（CON）组、 模拟缺血再灌注（CIR）组、 依折麦布（EIR） 组、 辛伐他汀 （SIR）组和依折麦布+辛伐他汀 （ESIR） 组， 分别予生理盐水或其溶解的药物灌胃 2 周后分离右室心肌细胞， 采用全细胞膜片钳技术记录 Ito。结果 （1） Ito电流密度 （+60 mV）： CIR 组较 CON 组下降， EIR 组与 CIR 组比较差异无统计学意义（P＞0.05）， SIR 组、 ESIR 组与 CIR 组比较均升高， SIR 组与 ESIR 组比较差异无统计学意义（P＞0.05）。（2）Ito稳态失活曲线最大半数失活电压（V1/2）： CIR 组较 CON 组显著增大， EIR 组与 CIR 组比较差异无统计学意义（P＞0.05）， SIR 组和 ESIR 组较 CIR 组均显著减小（P＜0.05）， SIR 组和 ESIR 组比较差异无统计学意义（P＞0.05）。斜率因子（K）各组间差异无统计学意义（P＞0.05）。（3）失活后恢复曲线失活时间常数（τ）值： CIR 组较CON 组显著增加， EIR 组与 CIR 组间差异无统计学意义 （P＞0.05）， SIR 组、 ESIR 组较 CIR 组明显减低 （P＜0.05）， 而SIR 组与 ESIR 组比较差异无统计学意义（P＞0.05）。结论 辛伐他汀、 依折麦布+辛伐他汀预处理可以逆转模拟缺血再灌注对心肌细胞 Ito的影响， 且效果相似， 而依折麦布未表现出这种效果。

关键词: 膜片钳术, 再灌注损伤, 依折麦布, 辛伐他汀, 瞬时外向钾电流

Abstract: Objective To observe the impact of alone or combined use of ezetimibe and simvastatin on transient outward potassium current (Ito) in ventricular myocytes of rat model of ischemia and reperfusion (IR). Methods Seventy-five male SD rats were randomly divided into five groups, control group (CON), control-IR group (CIR), ezetimibe treatment group (EIR), simvastatin treatment group (SIR) and combined ezetimibe and simvastatin treatment group (ESIR). After two weeks of treatment with intragastic normal saline or drugs (ezetimibe or simvastatin), myocytes were isolated from right ventricular with collagenase Ⅱ, and Ito was recorded by whole-cell patch clamp technique. Results (1) The Ito current density at +60 mV was significantly decreased in CIR group than that of CON group (P＜0.05). There was no significant difference in Ito current density between SIR group and ESIR group (P＞0.05). The Ito current densities were higher in SIR group and ESIR group compared to those of CIR group. There was no significant difference in Ito current density between SIR group and ESIR group (P＞0.05). (2) There was a significant increase in the half-inactivation (V1/2) in CIR group than that of CON group, but no significant difference between EIR group and CIR group (P > 0.05). There was a significant difference in the half-inactivation (V1/2) in SIR group and ESIR group compared to that of CIR group (P＜0.05), but no significant difference between SIR group and ESIR group (P＞0.05). There was no significant difference in the slope factor (K) between five groups (P＞0.05). (3) The time-constant (τ) of Ito recovery curves from inactivation was significantly higher in CIR group than that of CON group (P＜0.05), which was no significant difference between EIR group and CIR group (P＞0.05). There was a significant difference in the time-constant (τ) of Ito recovery curves from inactivation in SIR group and ESIR group compared to that of CIR group (P＜0.05), but no
significant difference between SIR group and ESIR group (P＞0.05). Conclusion Simvastatin pre-treatment or ezetimibe +simvastatin pre-treatment can reverse the effect of IR on Ito of ventricular myocytes, but ezetimibe shows no such effects.

Key words: patch-clamp techniques, reperfusion injury, Ezetimibe, Simvastatin, transient outward potassium current