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|本期目录/Table of Contents|

低渗溶液通过激活KATP通道对大鼠缺血心肌的保护作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第4期
页码:
477-481,490
栏目:
基础研究
出版日期:
2010-06-10

文章信息/Info

Title:
Hypotonicity contributes to cardioprotection during ischemia/reperfusion injury by activating KATP channels
作者:
徐萌; 史路平; 张知非; 刘杰; 王军
首都医科大学生理学教研室，北京 100069
Author(s):
XU Meng;  SHI Lu-ping;  ZHANG Zhi-fei;  LIU Jie;  WANG Jun
Department of Physiology, Capital Medical University, Beijing 100069, China
关键词:
低渗溶液; KATP通道; 缺血/再灌注损伤; 大鼠
Keywords:
hypotonic solution;  KATP channel;  ischemia/reperfusion injury;  rat
分类号:
R331.38
DOI:
-
文献标识码:
A
摘要:
目的: 探讨低渗溶液通过激活KATP通道对大鼠缺血心肌的保护作用。方法： 用RT-PCR法检测大鼠心肌细胞上KATP通道内向整流性亚单位基因的表达。用膜片钳单通道记录方法，观察急性分离的大鼠心肌细胞在低渗溶液刺激下，钾离子电流的变化及电生理学特征。将大鼠心脏随机分为5组:缺血对照(CON)组、格列苯脲(glibenclamide，Glib)组、缺血预适应(IPC)组、低渗处理(HYPO)组和HYPO+Glib组，用Langendorff方法灌流离体大鼠心脏，分别记录各组左心室形成压(LVDP)和左心室等容期压力最大变化速率(±LVdP/dtmax)。观察低渗溶液对缺血心肌的保护作用。结果: ①RT-PCR检测证实，大鼠心肌细胞上KATP通道的Kir亚单位存在两种类型：Kir6.1与Kir6.2。②膜片钳单通道记录证实，低渗溶液的刺激可以激活电导为(30.34±1.76) pS的KATP通道电流(-80 mV)，开放概率(Po)明显增加(等渗溶液时为：0.01±0.01；低渗溶液时为：0.51±0.12)，该电流可被10 μmol/L的Glib阻断(Po降低为0.03±0.02，P<0.05)。③灌流实验证实，在一定条件下，与CON组相比，再灌注前给予缺血心脏低渗溶液灌流5 min可明显改善心脏的功能［再灌注60 min时，CON组的LVDP为缺血前的(45.02±1.70)%；而HYPO组的LVDP则升高至(58.43±0.86)%；+LVdP/dtmax由(42.85±4.45)%升高至(61.96±2.98)%；-LVdP/dtmax由(53.94±2.52)%升高至(66.60±3.86)%，均P<0.05］，且该保护作用可部分被10 μmol/L Glib阻断(P<0.05)。结论： 大鼠心肌细胞上的KATP通道具有容积敏感性，低渗溶液对大鼠缺血心肌的保护作用可能是通过激活KATP通道发挥作用。
Abstract:
AIM: To investigate the protective effect of hypotonicity that, against ischemic heart, may be activating KATP channel. METHODS: RT-PCR technique was used to detect the expression of Kir (inward rectifier potassium channel) genes in rat cardiac myocytes. Single-channel patch clamp technique was used to record the volume-sensitive potassium current of acutely isolated rat cardiac myocytes under hypotonic condition. Rat hearts were divided into five groups: 1) ischemia (CON) group, 2) glibenclamide (Glib) group, 3) ischemic preconditioning (IPC) group, 4) hypotonic solution treatment (HYPO) group and 5) hypotonic solution plus glibenclamide treatment (HYPO+Glib) group. Isolated rat hearts were Langendorff perfused and cardiac function was assessed by measuring the LVDP (left ventricular developed pressure) and ±LVdP/dtmax (maximal rate of left ventricular pressure development) to observe the protection effect of hypotonic solution to ischemic heart. RESULTS: Both Kir6.2 and Kir6.1 were expressed in the rat heart. In single cardiac myocytes, hypotonic solution activated an ATP-sensitive potassium (KATP) current with the single-channel conductance of (30.34±1.76) pS at 80 mV and the open probability (Po) increased from 0.01±0.01 to 0.51±0.12. The current was blocked by KATP channel blocker glibenclamide (10 μmol/L). Pre-perfusing the heart with hypotonic solution for 5 min before ischemia/reperfusion resulted in a significant improvement in heart function compared with that in CON group ［at 60 min of reperfusion, LVDP recovered from (45.02±1.70)% to (58.43±0.86)%, +LVdP/dtmax recovered from (42.85±4.45)% to (61.96±2.98)% and -LVdP/dtmax recovered from (53.94±2.52)% to (66.60±3.86)%; P<0.05］. The cardiac protective effect of hypotonicity was eliminated by Glib. CONCLUSION: KATP channels in rat cardiomyocytes have volume sensitivity and hypotonicity may contribute to the cardioprotection during ischemia/reperfusion injury by activating KATP channels.

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备注/Memo

备注/Memo:
收稿日期：2009-12-07.基金项目：国家自然科学基金项目资助(30670765)；北京市自然科学基金项目资助(7072010) 通讯作者：王军，教授，主要从事心血管电生理研究Email:wangjunbw@gmail.com 作者简介：徐萌，硕士生Email:xumeng850203@yahoo.com.cn
更新日期/Last Update: 2010-05-20