摘要
目的:比较K阿片受体激动剂U50488H预处理与远程预处理诱导心肌缺血耐受对心肌梗塞(MI)范围与心肌酶的影响。方法:32只雄性新西兰大白兔随机分成四组(各组8例):对照组、U50488H组、远程缺血预处理(RPC)组和选择性K阿片受体阻断剂(Nor-BNI)+U50488H组。对照组心肌缺血前1.5h静脉给予戊巴比妥钠30mg/kg;RPC组在心肌缺血前1.5h静脉给予戊巴比妥钠30mg/kg麻醉动物后,行双后肢短暂缺血预处理2次(充气式压力止血带环扎双后肢腘窝上1/3,压力26.6kPa,每次10min,间隔10min);U50488H组在心肌缺血前105min静脉注射U50488H1.5mg/kg,余同RPC组;Nor-BNI+U50488H组在预处理前15min给予Nor-BNI2mg/kg,余同U50488H组。各组最后制作急性心肌缺血模型:冠状动脉左前降支完全闭塞45min,松开结扎圈再灌注2h。依据美蓝、TTC组织染色,观察各实验组MI质量比、肌钙蛋白T、心肌酶的变化。结果:U50488H可模拟RPC对心肌的保护作用,较对照组明显减少心肌缺血-再灌注损伤所致的MI[(0.15±0.11)g∶(0.29±0.11)g],肌钙蛋白T[冠脉阻闭45min(3.86±1.19)ng/ml∶(9.16±2.82)ng/ml],心肌酶的含量,P均<0.01。该作用可被选择性K阿片受体阻断剂Nor-BNI所阻断。结论:RPC诱导心肌缺血耐受与K阿片受体激活具有密切关系,激活K阿片受体是RPC诱导心肌缺血耐受的机制之一。
Objective.. To study the effects of US0488H （a selective K-opioid receptor agonist） on the size of myocardial ischemic-reperfusion and the plasma contents of myocardium enzyme compared with the protection of remote ischemic preconditioning from myocardial isehemia in rabbits. Methods.. A total of 32 male New Zealand white rabbits were randomly divided into four groups： remote preconditioning group （RPC）, ischemia-reperfusion group （control）, U50488H group and K-opioid receptor blocking agent （Nor-BNI） ＋US0488H group respectively. The detailed experimental protocols were as following： Before left anterior descending coronary artery were occluded, animals in control group were anesthetized for 90min by pentobarbital sodium （SP） 30mg/g, while animals in RPC group were anesthetized with SP 30mg/g i. v and received both hind-limb ischemia preconditioning 2 times with obstructed by inflated blood pressure cuff keep on 200mmHg for 10min with 10min interval, then followed by 60min reperfusion; In U50488H group, all animals were injected U50488H 1.5mg/g before myocardial ischemia, then step as RPC group. In （Nor-BNI） ＋ U50488H group all animals were injected Nor-BNI 2mg/kg before myocardial ischmemia, then step as U50488H group. The model of myocardial ischmemia was made in the end of each group. Left anterior descending coronary artery was completely oceluded for 45min and followed by 2h reperfusion in all rabbits. The area on risk and the infarct size were determined by staining with methylene blue and triphenyl tetrazolium chloride （TTC） respectively. Results： Compared with control group, U50488H obviously decreased the infarct size [ （0. 29±0. 11） g vs. （0. 15±0. 11） g] and the content of serum troponin T [ （9.16±2. 82） ng/ml vs. （3. 86±1. 19） ng/ml] （P〈 0.01 all） and myocardium enzyme caused by myocardial ischemia reperfusion injury （P〈0.05 all）, which can be blocked by K-opioid receptor blocking agent Nor-BNI （P〈0.01, P〈0. 05）. Conclusion： The study showed that RPC pretrcatment and U50488H can protect the myocardium from ischemia reperfusion injury, decreases myocardial infarction size and reduces myocardial enzyme leakage, lowers serum troponinT concentration, K-opioid receptor agonism could be the one mechanism of RPC effect.
出处
《心血管康复医学杂志》
CAS
2010年第1期25-30,共6页
Chinese Journal of Cardiovascular Rehabilitation Medicine
基金
全军卫生科研基金资助(No.2006131001)
关键词
缺血预处理
心肌缺血
肌钙蛋白T
Ischemic preconditioning
Myocardial ischemia
Troponin T
