δ受体在氢吗啡酮后处理维持大鼠离体心脏缺血再灌注时电生理稳定性中的作用

Role of δ-opioid receptors in hydromorphone postconditioning-induced maintenance of electrophysiological stability during ischemia-reperfusion in isolated rat hearts

目的 评价δ受体在氢吗啡酮后处理维持大鼠离体心脏缺血再灌注时电生理稳定性中的作用.方法 健康雄性SD大鼠,2～3月龄,体重280～360 g,取成功建立Langendorff离体心脏灌注模型的心脏32个,采用随机数字表法分为4组（n=8）：对照组（C组）、心脏缺血再灌注组（I∕R组）、氢吗啡酮后处理组（HP组）和氢吗啡酮＋δ受体拮抗剂纳曲吲哚后处理组（HNP组）.采用全心停灌60 min 再灌注60 min的方法制备离体心脏缺血再灌注损伤模型.HP组和HNP组于再灌注即刻灌注含4.1 ng∕ml氢吗啡酮或含4.1 ng∕ml氢吗啡酮＋5 μmol∕L纳曲吲哚的K-H液10 min,然后灌注K-H液50 min.分别于平衡灌注20 min（T0）和再灌注10、25、60 min（T1-3）时,记录HR、左心室前壁内外膜层心肌90%单相动作电位时程（MAPD90）,并计算跨室壁复极离散度（TDR）,记录再灌注期间心律失常发生情况、心脏复跳时间和心律失常持续时间.结果 与C组比较,I∕R组和HP组T1,2时内膜层心肌MAPD90、T1时外膜层心肌MAPD90延长,HNP组T2,3时HR降低,T1-3时内膜层和外膜层心肌MAPD90延长,I∕R组T1时、HNP组T2时TDR增大,HP组T3时TDR减小（P〈0.05）;与I∕R组比较,HP组和HNP组心律失常评分差异无统计学意义（P〉0.05）,心脏复跳时间缩短,T1时TDR减少, HP组心律失常持续时间缩短,T1时内膜层心肌MAPD90缩短,HNP组T2,3时HR降低,T1-3时内外膜层心肌MAPD90延长,T2,3时TDR减少（P〈0.05）;与HP组比较,HNP组心脏复跳时间、心律失常持续时间和心律失常评分差异无统计学意义（P〉0.05）,T2,3时HR降低,T1-3时内膜层和外膜层心肌MAPD90延长,T3时TDR增大（P〈0.05）.结论 氢吗啡酮后处理维持大鼠离体心脏缺血再灌注时电生理稳定性的机制与激活δ阿片受体有关.

Objective To evaluate the role of δ-opioid receptors in hydromorphone postcondition-ing-induced maintenance of electrophysiological stability during ischemia-reperfusion（I∕R）in isolated rat hearts. Methods Healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 60 mg∕kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Thirty-two isolated hearts were divided into 4 groups after successful preparation of Langendorff perfusion model（n=8 each）using a random number ta-ble： control group（group C）, group I∕R, hydromorphone postconditioning group（group HP）and hydro-morphone plus δ-opioid receptor antagonist naltridole postconditioning group（group HNP）. In HP and HNP groups, the hearts were perfused for 10 min with K-H solution containing 41 ng∕ml hydromorphone and 41 ng∕ml hydromorphone plus 5 μmol∕L naltridole, respectively, and then with K-H solution for 50 min. At 20 min of stabilization（T0）and 10, 25 and 60 min of reperfusion（T1-2）, heart rate（HR）, monophasic action potential（MAP）duration at 90% repolarization（MAPD90）of the two layers（endocar-dium, epicardium）of the anterior left ventricular wall were recorded. Transmural dispersion of repolariza-tion（TDR）was calculated. The development of arrhythmia, time for restoration of spontaneous heart beat and duration of arrhythmia were recorded during the period of reperfusion. Results Compared with group C, MAPD90of endocardium at T1-2and MAPD90of epicardium at T1were significantly prolonged in I∕R and HP groups, HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3in group HNP, TDR was significantly enlarged at T1in group I∕R and at T2in group HNP, and TDR was decreased at T3in group HP（P〈0.05）. Compared with group I∕R, no significant change was found in arrhythmia score（P〉0.05）, the time for restoration of spontaneous heart beat was significantly shortened, and TDR was decreased at T1in HP and HNP groups, duration of arrhythmia was significantly shortened, and MAPD90of endocardium was shortened at T1in group HP, and HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was decreased at T2-3in group HNP（P〈0.05）. Compared with group HP, no significant change was found in time for restoration of spon-taneous heart beat, duration of arrhythmia or arrhythmia score（P〉0.05）, HR was significantly decreased at T2-3, MAPD90of endocardium and epicardium was prolonged at T1-3, and TDR was increased at T3in group HNP（P〈0.05）. Conclusion The mechanism underlying hydromorphone postconditioning-induced maintenance of electrophysiological stability during I∕R is related to activating δ-opioid receptors in isolated rat hearts.