【摘要】 目的探讨血管紧张素转换酶抑制剂（ACEI）和阈下缺血预处理联合预处理诱导的心肌保护作用中mi-toK_ATP通道激动后的作用机制。方法采用离体大鼠心脏Langendorff灌流模型,观察心脏电脱耦联发生时间、细胞膜Na+/K+-ATPase和Ca2+/Mg2+-ATPase活性的改变。结果单独使用卡托普利、或给予大鼠心脏2min缺血/10min复灌作为阈下缺血预处理,均不能改善长时间缺血/复灌引起的心脏收缩功能下降。而卡托普利和阈下缺血预处理联合使用可增高心脏收缩功能。mitoK_ATP通道特异性阻断剂5-HD可取消这一联合预处理的作用。联合预处理可引起缺血后电脱耦联发生时间延长,缺血心肌细胞膜Na+/K+-ATPase和Ca2+/Mg2+-ATPase活性增高;5-HD可取消此作用。结论mitoK_ATP通道参与了联合预处理延迟缺血引起的细胞间脱耦联和促进细胞膜离子通道稳定性维持的作用。更多还原

【Abstract】 Aim: To determine mechanisms of cardioprotection induced by combination angiotensin-converting enzyme inhibitors(ACEI)with subthreshold preconditioning after activation of mitochondrial ATP-sensitive potassium(mitoK ATP )channel. Methods: The Langendorff model of isolated rat heart was used. The time of the onset of uncoupling, the activities of sarcolemmal Na+/K+ -ATPase and Ca 2+ /Mg 2+ -ATPase were measured. Results: The subthreshold preconditioning (2 min of ischemia and 10 min reperfusion) or captopril(an ACEI) alone did not protect hearts against injury of sustained ischemia. However combination captopril with subthreshold preconditioning increased LVDP. Pretreatment hearts with mitoK ATP channel inhibitor 5-HD abolished the protection effect. Combination captopril with subthreshold preconditioning delayed the onset of uncoupling, and enhanced the activities of sarcolemmal Na+/K+ ATPase and Ca 2+ /Mg 2+ -ATPase in ischemia/reperfusion hearts. But 5-HD cancelled these cardioprotection effects. Conclusion: Combination ACEI with subthreshold preconditioning delays the onset of cellular uncoupling induced by acute ischemia, and promotes the stability of sarcolemmal ion channels, in which activation of the mitoK ATP channels may be involved.更多还原