摘要
目的:研究血红素氧化酶1(HO-1)在对抗心肌缺氧-复氧损伤中的作用,并探讨环氧化酶2(COX-2)是否参与其作用机制。方法:采用离体大鼠心脏Langendorff灌流模型,观察心功能和酶学等指标。结果:(1)HO-1的诱导剂高铁血红素可明显抑制缺氧-复氧心脏LVEDP增高,LVDP和±dp/dtmax的下降;减少复氧期LDH释放,缩小心肌梗死面积(P<0·01)。(2)HO-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)GC的抑制剂亚甲蓝和COX-2的抑制剂塞来昔布均可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,其作用可能通过激动鸟苷酸环化酶途径,继而调节COX-2的活性来完成。
AIM： To investigate the role of HO- 1 in protection of rat hearts against anoxia/reoxygenation - injury and its underlying mechanism. METHODS： Cardiac contractility, lactate dehydrogenase （LDH） and infarct area were analyzed by the Langendorff method in isolated rat hearts. RESULTS： After intraperitoneal injection of HO- 1 inducer heroin, CO concentration in rat blood enhanced （ P 〈 0.01 vs control group）. Pretreatment with heroin prevented the increase in LVEDP and decrease in LVDP, ±dp/dtmax during the anoxia and reoxygenation period in hearts. Heroin had no effect on changes of coronary flow, but it really inhibited the release of LDH from anoxia/reoxygenation hearts. Heroin also reduced the 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 vs control group）. ZnPP aggravated the decrease in LVDP and =e dp/dtmax. Compared with anoxia/reoxygenation heart, pretreatment of ZnPP enhanced the LDH release and enlarged the infarct area （ P 〈0.05）. GC inhibitor methylene blue and cyclooxygenase- 2 （COX - 2） inhibitor celecoxib both partly abolished the protection effect of heroin on LVEDP, LVI）P and =e dp/ dtmax. Ptetreatment of methylene blue or celecoxib also cancelled the inhibition of LDH release and reduction of infarct area caused by heroin （ P 〈 0.05）. CONCLUSION： HO - 1 inducer hemin protects heart from anoxia/reoxygenation - induced injury. The cardiac protection of HO/CO might be through GC pathway, and the activation of COX- 2 might be also involved in this process.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2006年第6期1087-1091,共5页
Chinese Journal of Pathophysiology
基金
温州市科技局科研基金资助项目(No.S2001A52)
