环氧化酶-2参与血红素氧化酶1对抗大鼠心肌缺氧-复氧的损伤  

Involvement of COX-2 in antagonism to heme oxygenase-1 on cardioprotection from anoxia/reoxygenation induced injury in rats

作　　者：汪洋[1] 徐和靖[2] 王万铁[1] 陈莹莹[3] 沈岳良[3] 杜友爱[2] 

机构地区：[1]温州医学院病理生理教研室,浙江温州325035 [2]温州医学院生理教研室,浙江温州325035 [3]浙江大学医学院生理教研室,浙江杭州310006

出　　处：《基础医学与临床》2007年第7期758-762,共5页Basic and Clinical Medicine

基　　金：浙江省教育厅科研基金(20041076);温州市科技局科研基金(Y2005A025)

摘　　要：目的研究环氧化酶-2是否参与血红素氧化酶1(HO-1)对抗大鼠心肌缺氧-复氧的损伤及其可能的机制。方法采用离体大鼠心脏Langendorff灌流法观察左室舒张末压(LVEDP)、左室发展压(LVDP)和最大左室收缩、舒张速率(±dp/dtmax)。用全自动生化分析仪分析冠脉流出液乳酸脱氢酶(LDH)释放量。应用双波长分光光度计法间接测定大鼠血中COHb含量。心脏冷冻切片法观察心肌梗死面积。用6-keto-PGF1αRIAkit测定样本中前列腺素I2(PGI2)的稳定产物6-keto-PGF1α的含量。结果①HO-1的诱导剂高铁血红素明显抑制缺氧-复氧心脏LVEDP增高,降低LVDP和±dp/dtmax;减少复氧期LDH释放,缩小心肌梗死面积(P<0.01)。②HO-1的抑制剂可加重缺氧-复氧心脏LVDP和±dp/dtmax下降,LDH释放和梗死面积明显高于单纯缺氧-复氧组(P<0.05)。③环氧化酶-2(COX-2)抑制剂塞来昔布有部分取消高铁血红素降低缺氧-复氧心脏LVEDP、增加LVDP和±dp/dtmax的作用,使LDH的释放和梗死面积明显增加(P<0.05)。结论诱导HO-1增加可保护缺氧-复氧心肌,其作用可能通过调节COX-2的活性来完成。Objective To investigate the role of HO-1 in the protection of rat heart from anoxia/reoxygenation induced injury and its underlying mechanism. Methods LVEDP, LVDP and dp/dtmax were analyzed by the Langendorff method in isolated rat heart. Lactate dehydrogenase （LDH）, infarct area, COHb and 6-keto-PGF1α were further determined in the experiment. Results After intraperitoneal injection of HO-1 inducer hemin, CO concentration in rat blood enhanced （P 〈0. 01 compared with control group）. Pretreatment of hemin prevented the increase in LVEDP and decrease in LVDP, ±dp/dtmax during the anoxia and reoxygenation period in hearts. Hemin had no effect on change of coronary flow, but it did inhibit the release of LDH from anoxia/reoxygenation heart. Hemin also reduced infarct area in anoxia heart after 2 h-reoxygenation （P 〈0. 01 ）. CO concentration in rat blood reduced after intraperitoneal injection of HO-1 inhibitor ZnPP （P 〈0. 01 compared with control group）. ZnPP aggravated the decrease in LVDP and dp/dtmax. Pretreatment of ZnPP enhanced the LDH release and enlarged the infarct area （ P 〈 0. 05 ）. Cyclooxygenase-2 （COX-2） inhibitor celecoxib partly abolished the protection effect of hemin on LVEDP, LVDP and dp/dtmax. Pretreatment of celecoxib could also cancel the inhibition of LDH release and reduction of infarct area caused by hemin （P 〈 0. 05 ）. Conclusion HO-1 inducer hemin may protect heart from anoxia/reoxygenation induced injury. The activation of COX-2 may be also involved in the cardiac protection of HO/CO.

关 键 词：心脏 缺氧-复氧 血红素氧化酶-1 环氧化酶-2 

分 类 号：R363[医药卫生—病理学]