【摘要】 目的:研究血红素氧化酶1的诱导剂高铁血红素在对抗大鼠心肌缺血-复灌损伤中的作用及其相应机制。方法:利用离体大鼠心脏Langendorff灌流模型,观察心功能、心肌梗死面积等指标的变化。结果:腹腔注射高铁血红素后24 h,可明显改善缺血-复灌心脏(30 m in缺血/2 h复灌)的收缩功能,减少复灌期乳酸脱氢酶(LDH)和肌酸磷酸(CK)的释放,缩小心肌梗死面积。在腹腔注射高铁血红素前给予线粒体KATP通道阻断剂5-HD或肌膜KATP通道阻断剂HMR-1098均可取消高铁血红素引发的心肌保护作用。在高铁血红素预处理后24 h,缺血/复灌前10 m in给予K ca通道阻断剂pax illine,与高铁血红素组相比,心肌梗死面积扩大,心脏收缩功能下降。结论:高铁血红素预处理可对抗心肌缺血-复灌性损伤,其作用可能与激活KATP通道和K ca通道有关。更多还原

【Abstract】 Objective: To investigate the effects of heme oxygenase 1 inducer hemin on protection of ischemia-reperfusion injury in rats and its mechanisms.Methods: The Langendorff model of isolated rat heart was used;the left anterior descending coronary artery was occluded for 30 min and subsequently reperfused for 2 h.Then the ventricular function and infarct size were measured.Results: Hemin preconditioning prevented the increase in LVEDP,decrease in LVDP and ±dp/dt_max in the isolated ischemia-reperfusion rat hearts.The leakage of LDH and CK in the coronary effluent was significantly declined in hemin-treated rat hearts.And the infarct size was also reduced.Administration of a blocker of mitochondrial ATP-sensitive potassium channel(mitoK_ATP) 5-HD（5 mg/kg） before hemin preconditioning increased the LVEDP,and reduced the LVDP and ±dp/dt_max.The leakage of LDH and CK in the coronary effluent and the infarct size were also increased compared with only hemin-treated rat hearts.Pretreatment of the rats with a blocker of sarcolemmal ATP-sensitive potassium channel(sarcK_ATP) HMR-1098（6 mg/kg） before hemin preconditioning also abolished the protective effect.Infusion of paxilline（1 μmol/L）,a blocker of calcium activated potassium channel(K_Ca) for 10 min before ischemia/reperfusion led to larger infarct size and poorer myocardial performance as compared with the hemin group.The leakage of LDH and CK in the coronary effluent was also increased.Conclusion: Both mitoK_ATPand sarcK_ATPchannels activation are required for the delayed cardioprotection induced by hemin.The opening of K_Ca channels-dependent mechanism may be involved in the protection.更多还原