【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。更多还原

【Abstract】 Objective: To investigate whether cyclooxygenase-2（COX-2） and heme 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（40 μg/kg）,and the isolated hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion 24 h later.Bradykinin pretreatment would improve post-ischemic 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（20 μg/kg） before bradykinin partially abrogated the delayed protection.Pretreatment with the mitochondrial ATP sensitive potassium channel(mitoK_ATP) 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 mitoK_ATP channel may serve as both a trigger and a mediator in the cardioprotection.更多还原