抑制磷脂酰肌醇-3激酶通路减弱乙醇后处理的心肌保护作用

目的: 探讨抑制磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI3K)途径是否减弱乙醇后处理的心肌保护作用。方法: 采用离体大鼠心脏Langendorff灌注方法,局部结扎冠状动脉左前降支30 min,再灌注120 min复制心肌缺血/再灌注模型。测定心室动力学指标和再灌注期间冠状动脉流出液中乳酸脱氢酶(lactate dehydrogenase,LDH)含量。结果: 与单纯缺血/再灌注相比,乙醇后处理明显促进了左心室发展压、左心室内压最大上升和下降速率、左心室做功量的恢复,降低再灌注期冠状动脉流出液中LDH的释放(P < 0.01);PI3K抑制剂渥曼青霉素减弱了乙醇后处理的作用,抑制了心室动力学指标的恢复(P <0.05~P < 0.01),LDH释放增多(P < 0.01)。结论: 抑制PI3K通路减弱了乙醇后处理的心肌保护作用。

Inhibition of phosphatidylinositol 3-kinase pathway attenuated the cardioprotection of ethanol postconditioning in isolated rat hearts

Objective：To investigate whether the cardioprotection of ethanol postconditioning can be attenuated by inhibition of phosphatidylinositol-3 kinase（PI3K） pathway in isolated rat hearts subjected to ischemia and reperfusion.Methods：Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 minutes of regional ischemia（occlusion of left anterior descending artery） followed by 120 minutes of reperfusion.The ventricular hemodynamic parameters and lactate dehydrogenase（LDH） release during reperfusion were measured.Results：In contrast to ischemia and reperfusion,ethanol postconditioning improved the recovery of left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure,rate pressure product and reduced LDH release during reperfusion（P0.01）.Administration of PI3K inhibitor wortmannin attenuated the effect of ethanol postconditioning,the recovery of hemodynamic parameters were inhibited（P0.05-P0.01）,LDH release was increased（P0.01）.Conclusions：These findings indicate that inhibition of PI3K pathway can attenuate the cardioprotection of ethanol postconditioning.