【摘要】 目的:观察κ-阿片受体激动剂U 50488H预处理(U 50488H pretreatm ent,UP)诱发的早期和延迟性心肌保护作用,以及环氧化酶-2(cyclooxygenase-2,COX-2)是否中介了此过程。方法:应用离体Langendorff灌流心脏和缺血/复灌模型,评价U 50488H的心脏保护作用。结果:U 50488H预处理大鼠24 h后,可明显改善心肌缺血后的复灌期内LVEDP的抬高,以及LVDP和±dP/dtm ax的下降(P<0.05);大鼠心脏梗死面积以及LDH和CK的释放量较单纯缺血对照组明显降低(P<0.01)。而在心脏缺血前1 h给予U 50488H,同样可增强心肌对抗缺血/复灌性损伤的能力。U 50488H预处理30m in后,使用COX-2的抑制剂塞来昔布并不能阻断U 50488H诱发的早期心肌保护作用,但该药可取消U 50488H诱发的延迟性心肌保护作用,表现在LVEDP明显高于单纯U 50488H 24 h处理组(UP24h组,P<0.01),LVDP和±dP/dtm ax则明显低于UP 24 h组(P<0.05),心肌梗死面积、LDH和CK的释放量也显著高于UP24h组(P<0.05)。结论:U 50488H具有心肌保护作用,COX-2中介了κ-阿片受体激动剂的延迟性心肌保护作用,而并不参与其早期心肌保护作用。更多还原

【Abstract】 Objective: To determine whether U50488H,a selective agonist of κ-opioid receptor,could induce biphasic（early and late） cardioprotection against myocardial ischemia/reperfusion injury and to explore the underlying mechanisms.Methods: Isolated perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion and the cardiac function was evaluated.Results: Left ventricular end-diastolic pressure（LVEDP）,left ventricular developed pressure（LVDP） and maximal velocity of contraction and relaxation(±dP/dt_max) were improved when U50488H was administered 1 or 24 h before ischemia（P<0.05）.Myocardial infarct size,activities of creatine kinase（CK） and lactate dehydrogenase（LDH） in the coronary effluent were lower in the U50488H pretreatment group than those in the control group.Administration of a selective cyclooxygenase-2（COX-2） inhibitor,celecoxib abolished the late phase of cardioprotection produced by administration of U50488H 24 h before ischemia.Activities of CK and LDH in the coronary effluent were higher in U50488H and celecoxib co-pretreatment group than those in U50488H group.However,administration of celecoxib did not block the early phase of cardioprotection by 1 h treatment of U50488H before ischemia.Conclusion: The late（but not the early） phase of cardioprotection induced by κ-opioid receptor agonist might be mediated by COX-2.更多还原