COX-2和HO-1参与缓激肽诱发的晚期心肌保护作用  

COX-2 and HO-1 are involved in the delayed preconditioning elicited by bradykinin in rat hearts

作　　者：董海正[1] 陈莹莹[1] 朱立[1] 徐和靖[1] 汪洋[2] 沈法荣[3] 蔡朱男[1] 沈岳良[1] 

机构地区：[1]浙江大学医学院生理学系,浙江杭州310058 [2]温州医学院生理学教研室,浙江温州325027 [3]浙江医院心内科,浙江杭州310013

出　　处：《浙江大学学报（医学版）》2007年第1期13-20,共8页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(30400094);浙江省教育厅科研基金(20041076)

摘　　要：目的:观察环氧化酶2(COX-2)和血色素氧化酶-1(HO-1)是否参与缓激肽诱发的晚期心肌保护作用。方法:在整体给药后24 h,采用大鼠离体心脏Langendorff灌流方法,以结扎冠脉前降支30 m in复灌2 h作为缺血/复灌,期间观测心脏收缩功能、乳酸脱氢酶(LDH)和心肌梗死面积等指标。结果:①SD大鼠静脉注射缓激肽(40μg/kg)24 h后,可促进缺血/复灌心脏收缩功能的恢复,减少LDH释放,缩小心肌梗死面积。②缓激肽注射之前预先给予COX-2抑制剂塞来昔布(3m g/kg)组,与单纯给予缓激肽组相比,左室舒张末压增高,左室发展压、最大左室收缩/舒张速率降低,而LDH释放量和心肌梗死面积增加。③HO-1抑制剂ZnPP IX(20μg/kg)可部分取消缓激肽引起心功能的改善、LDH释放量的减少和心肌梗死面积的缩小。④在缓激肽注射前或后给予线粒体ATP敏感性钾离子通道(m itoKATP)阻断剂5-HD,均可取消缓激肽诱发的心肌保护作用。结论:COX-2和HO-1参与了缓激肽诱发的晚期心肌保护作用,而m itoKATP通道在缓激肽诱导的晚期心肌保护作用中扮演了触发器和通路终末效应器双重角色。Objective： To investigate whether cyclooxygenase-2（COX-2） and heine oxygenase-1 （HO-1） are involved in the bradykinin-induced delayed protection. Methods： Cardiac contractility,lactate dehydrogenase （LDH） and infarct area were analyzed in isolated rat hearts undergoing ischemia-reperfusion injury induced by Langendorff method. Results： Conscious rats received bradykinin （40μg/kg）, and the isolated hearts were subjected to 30 rain of regional ischemia and 120 rain of reperfusion 24 h later. Bradykinin pretreatment would improve postischemic performance,and reduced the release of LDH and infarct size. COX-2 inhibitor celecoxib （3 mg/kg） abolished bradykinin-induced protection,leading to poorer myocardial performance, release of more LDH and larger infarct sizes. Administration of HO-1 inhibitor ZnPP IX（20μg/ kg ） before bradykinin partially abrogated the delayed protection. Pretreatment with the mitochondrial ATP sensitive potassium channel （mitoKATP） antagonist 5-HD before or 24h after bradykinin administration also abolished the effect of protection. Conclusion. The results indicate that activation of HO-1 and COX-2 might be involved in the delayed cardioprotection evoked by bradykinin, and mitOKATP channel may serve as both a trigger and a mediator in the cardioprotection.

关 键 词：缓激肽/药理学 氧化还原酶类 心肌 心肌再灌注损伤/病理生理 钾通道 心肌再灌注损伤/预防和控制 

分 类 号：R54[医药卫生—心血管疾病]