二氮嗪对大鼠心肌线粒体膜电位及呼吸功能的影响

Effects of diazoxide on membrane potential and respiration function of rat cardiac mitochondria

目的 :研究二氮嗪对大鼠心肌线粒体功能的影响 ,以探讨其心肌保护作用的可能机理。方法 :以罗丹明 12 3为荧光探针测定线粒体膜电位 ,氧电极法测线粒体呼吸 ,观察二氮嗪对正常大鼠心肌线粒体跨膜电位及呼吸的影响。结果 :5 0 μmol·L-1的二氮嗪可引起线粒体膜电位去极化 ,此影响可被钾通道阻滞剂消除 ;二氮嗪 10 0 μmol·L-1可降低大鼠心肌线粒体琥珀酸链的R3、R4速率 ,但不影响呼吸控制率。结论 :二氮嗪可调节大鼠心肌线粒体功能 ,这与其抗心肌缺血保护作用有关。

AIM: To study the effects of selective mitoK_ ATP opener diazoxide on the isolated mitochondria from rat hearts and to discuss its cardioprotective mechanism. METHODS: Using Rhodamine123 (Rh123) as fluorescent prober to measure mitochondrial membrane potential and to record mitochondrial respiratory parameters with a Clark electrode,the effect of diazoxide on mitochondrial membrane potential and mitochondrial respiration were investigated. RESULTS: 50 μmol·L -1 diazoxide could induce mitochondrial membrane depolarization and this effect was abolished by application of a K_ ATP channel blocker. It could decrease R3 and R4 while oxidizing FAD-dependent substrates (succinate) but did not affect respiratory control ratio (RCR). CONCLUSION: Modulation by diazoxide on functions of rat cardiac mitochondria is associated with its anti-ischemic efficacy.