κ-阿片受体介导缺血后处理的心肌保护作用及其受体后机制  

κ-Opioid receptor mediates the cardioprotective effect of ischemic postconditioning

作　　者：王珏[1] 高琴[2] 沈佳[2] 叶挺梅[3] 夏强[2] 

机构地区：[1]浙江医学高等专科学校生理学教研室,浙江杭州310053 [2]浙江大学医学院生理学系,浙江杭州310058 [3]浙江丽水学院,浙江丽水323000

出　　处：《浙江大学学报（医学版）》2007年第1期41-47,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省科技厅基金(2005C30026);浙江医学高等专科学校自然科学基金(2005XZ02)

摘　　要：目的:探讨κ-阿片受体是否参与缺血后处理的对抗心肌缺血/复灌(I/R)损伤和心肌细胞缺氧/复氧(H/R)损伤的作用及其机制。方法:采用离体大鼠心脏Langendorff灌流模型,全心停灌30 m in、复灌120 m in复制I/R模型,测定心室力学指标和复灌各时点冠脉流出液中乳酸脱氢酶(LDH)含量。实验结束测定心肌组织form azan含量。酶解分离的心肌细胞采用缺氧60 m in、复氧60m in复制H/R模型,测定心肌细胞存活率。结果:在离体心脏模型上,与I/R组相比,缺血后处理组心肌组织的form azan含量明显增高,复灌期间冠脉流出液中LDH含量明显降低,同时缺血后处理明显改善心室力学指标,缓解冠脉流量的减少;在分离心肌细胞模型上,缺氧后处理明显提高心肌细胞存活率。κ-阿片受体阻断剂nor-b inaltorph im ine(nor-BN I)和线粒体ATP敏感性钾通道(m itoKATP)阻断剂5-hydroxydecanoate(5-HD)在离体大鼠心脏模型和分离心肌细胞模型上均能明显减弱缺血后处理的作用。同时在心肌细胞模型上,与H/R组相比,κ-阿片受体激动剂U 50488H明显提高心肌细胞存活率,其作用可被m itoKATP阻断剂5-HD所阻断。结论:缺血后处理具有抗心肌缺血/复灌损伤的作用,这种保护作用可能与其激活κ-阿片受体和m itoKATP有关。Objective： To investigate the effect of κ-Opioid receptors in the cardioprotection elicited by ischemic postconditioning and the underlying mechanism. Methods： The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30min of global ischemia followed by 120min of reperfusion, formazan content of myocardium was measured spectrophotometrically,and the level of lactate dehydrogenase （LDH） in the coronary effluent was also measured. In isolated ventricular myocytes hypoxia postconditioning was achieved by 3 cycles of 5 min reoxygenation/5 min hypoxia starting at the beginning of reoxygenation, and cell viability was measured. Results： In the Langendorff perfused rat heart model, ischemic postconditioning （6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion） increased formazan content, reduced LDH release,improved the recovery of the left ventricular developed pressure ,maximal rise/fall rate of left ventricular pressure,left ventricular end-diastolic pressure and rate pressure product（left ventricular developed pressure multiplied by heart rate）,attenuated the decrease of coronary flow during reperfusion and increased the isolated cell viability. Pretreatment with nor-BNI, an antagonist of κ-Opioid receptors and mitoKATP blocker 5-HD attenuated the effect of ischemic/hypoxic postconditioning. Conclusion： Postconditioning may protect myocardium against ischemia/reperfusion injury via activating κ-Opioid receptors and mitoKATP.

关 键 词：缺血预处理/预防和控制 受体 阿片样 心肌再灌注损伤/病理生理学 钾通道/药物作用 心肌缺血 模型 动物 

分 类 号：R541[医药卫生—心血管疾病]