钾通道开放剂对离体兔心缺血再灌注损伤的保护作用  

Protective effects of ATP-sensitive potassium channel openes on ischemia/reperfusion injury in isolated rabbit hearts

作　　者：许铁[1] 叶英[1] 吕建农[1] 

机构地区：[1]徐州医学院附属医院急救中心,徐州市221002

出　　处：《中国介入心脏病学杂志》2005年第6期391-394,共4页Chinese Journal of Interventional Cardiology

摘　　要：目的观察非选择性三磷酸腺苷敏感性钾(KATP)通道开放剂Pinacidil和线粒体型KATP(mitoKATP)通道开放剂Diazoxide预处理对高钾停跳离体兔心缺血再灌注损伤的保护作用,以及mitoKATP通道阻断剂5-hydroxydecanoic acid sodiumsalt(5HD)应用后其心肌保护作用的变化。方法采用离体兔心Langendorff灌注实验模型。离体兔心40只随机等分成5组(n=8):对照组(C组)、Pinacidil组(P组)、Diazoxide组(D组)、5HD+Pinacidil组(HP组)和5HD+Diazoxide组(HD组)。离体兔心用标准Thomas停搏液(4℃,K+16mmol/L)至心停跳,45min后再灌注20min,于心脏停跳前灌注药物15min,对比观察Pinacidil、Diazoxide及其与5HD合用时对再灌注后心功能及冠状动脉血流的影响以及再灌注末心肌超微结构、蛋白含量、脂质过氧化物丙二醛(MDA)以及腺苷酸含量的变化。结果再灌注后P组、D组、HP组心功能的恢复率均明显高于C组,心肌MDA的含量、蛋白的漏出量明显低于C组,超微结构观察损伤较轻;但HP组心功能的恢复要差于P组,心肌MDA的含量、蛋白的漏出量明显高于P组;HD组与C组各检测指标比较差异无统计学意义。结论Pinacidil(10μmol/L)和Diazoxide(30μmol/L)预处理对离体兔心缺血/再灌注心肌具有保护效果,且其保护效果可以部分被5HD所阻断,提示心肌mitoKATP通道可能是产生心肌保护作用的靶点之一。Objective To investigate the protective effects of different ATP-sensitive potassium （KATP） channel openers. Pinacidil and Diazoxide, on myocardium injury in isolated rabbit hearts caused by ischemia/ reperfusion and the possible changes after application of ATP-sensitve potassium channel blocker, 5-HD. Methods Observation was made on rabbit hearts peffused with a Iangendorff apparatus. Forty rabbits were randomly divided into five respective groups： 1. Pinacidil （Group P）, 2. Diazoxide （Group D）, 3. 5-HD ＋ Pinacidil （Group HP）, 4. 5-HD＋ Diazoxide （Group HD） and 5. the control （Group C）. All groups were subjected to 40 minutes of occlusion, followed by 20 minutes of reperfusion as cardiac arrested by cold cardioplegia. Any one of Pinacidil, Diazoxide , Pinaeidil or Diazoxide mixed with 5-HD was infused 15 minutes before cardioplegic heart rested in the experimental group. Cardiac tissue ultrastructure, hemadynamics variables, levels of adenine nucleotides and lipid peroxide of the myocardium were measured. Results （1） In Group P, Group D and Group liP, the recovery of myocardial contractility and heart rate after repeffusion was faster but MDA level and the amount of albumen released were lower than Group C. Moreover levels of myocardial adenosine triphosphate （ATP） were much higher compared with Group C. （2） In Group HP the recovery of myocardial contractility and heart rate was not as good as Group P, but its myocardium MDA level and amount of albumen released was higher than group P. Cone.htsion ATP-sensitive Potassium Channel openes may enhance myocardial protection against iscbemia / reperfusion injury. The above effect of myocardial protection was only partially closed down by ATP-sensitive potassium channel blocker： 5-HD. The mitoKATp channels on myocardium may be an important pathway of protection during ischemidreoeffusion process.

关 键 词：钾通道 再灌注损伤 心肌缺血 

分 类 号：R657.3[医药卫生—外科学] R654.2[医药卫生—临床医学]