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。
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/dtmax） 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.
出处
《浙江大学学报（医学版）》
CAS
CSCD
2006年第2期165-171,共7页
Journal of Zhejiang University(Medical Sciences)
基金
国家自然科学基金(30400094)
金华市科技局科研基金(03-2-331)
