【摘要】 目的 :研究缺血预处理 (IPC)延缓心肌细胞间电脱耦联现象及其可能的机制 ,尤其是线粒体膜ATP敏感性钾通道 (mitoKATP)在其中的作用。方法 :大鼠心脏Langendorff离体灌流 ,用四电极法测量心肌整体阻抗 (Rt) ,监测Rt 在心肌缺血后的变化来判断心肌细胞发生电脱耦联的时间。结果 :(1)对照组心肌缺血 40min后复灌 3 0min ,心肌细胞间电脱耦联发生平均时间为 (13 2 9± 0 95)min ;(2 )IPC可以明显延迟电脱耦联的发生时间、促进心肌缺血复灌后收缩功能的恢复 ;(3 )IPC前给予mitoKATP特异阻断剂 5-hydroxydecanoate(5-HD ,10 0 μmol/L)取消了IPC的心脏作用 ;(4)MitoKATP特异开放剂diazoxide(60 μmol/L)预处理可以模拟IPC延迟电脱耦联、促进心肌收缩功能恢复 ;(5)Diazoxide的IPC模拟作用能被 5-HD取消 ,也能被L型钙通道特异阻断剂verapamil(2 0 μmol/L)和自由基清除剂N -(2 -mercaptopropionyl)glycine(3 0 0 μmol/L)取消。 结论 :IPC可以通过激活mitoKATP延缓大鼠心肌缺血造成的细胞间电脱耦联和改善心肌收缩功能更多还原

【Abstract】 AIM: To test whether ischemic preconditioning (IPC) del ays ischemia-induced electrical uncoupling by activation of mitochondrial ATP-se nsitive potassium channels (mitoK ATP ). METHODS: Adult rat hearts perfused on a Langendorf f apparatus were subjected to 40 min ischemia followed by 30 min reperfusion. C han ges in coupling were monitored by measuring whole-tissue resistance. RES ULTS: IP C delayed the onset of uncoupling campared to ischemic control; Blocking mitoK ATP channels before the IPC protocol abolished the delay of uncoupling. The specif ic mitoK ATP channel opener diazoxide mimicked the protective effect of IPC . The delay induced by diazoxide was reduced by 5-HD, L-type Ca 2+ channel inhibitor verapamil and a free radical scavenger N-(2-mercaptopropionyl)glycine. CONCLUSIONS: IPC delays the onset of cellular electrical uncoup ling induced by acute ischemia, in which activation of the mitoK ATP channe ls may be involved.更多还原