AMPK抑制剂P5499拮抗无钙预处理心肌保护作用  

Blunting effects of AMPK inhibitor P5499 on the cardioprotection of brief calcium depletion preconditioning

作　　者：姚远[1] 毕生辉[2] 冯建宇[2] 时全星[1] 张建英[1] 周京军[1] 裴建明[1] 

机构地区：[1]第四军医大学生理学教研室,陕西西安710032 [2]第四军医大学西京医院心血管外科,陕西西安710032

出　　处：《心脏杂志》2012年第1期12-16,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(30971196)

摘　　要：目的:观察腺苷酸活化的蛋白激酶(AMPK)抑制剂P5499对短暂无钙预处理心肌保护作用的影响。方法:对健康SD雄性大鼠心脏行Langendorff离体灌流,实验全程记录心脏冠脉流量(CF)、左心室内压(LVP)、左室舒张末压(LVEDP)、室内压最大变化速率(±dp/dtmax)及心率(HR),并计算左室发展压(LVDP)和心率-压力乘积(RPP)评价心功能的变化。再灌注结束后,采用2、3、5-氯化三苯基四氮唑(TTC)染色法评价心肌梗死(MI)面积的变化。结果:缺血/再灌注(I/R)后,心功能显著降低,CF明显减少(P<0.01),MI面积的比率为(39.6±1.49)%。短暂无钙预处理(CPC)可使LVEDP明显降低(P<0.05),CF、LVDP、±dp/dtmax及RPP均明显改善(P<0.01),MI面积显著缩小(P<0.01)。缺血前单独给予P5499对心功能、CF及MI面积无明显影响,但其可显著逆转CPC的心肌保护作用(P<0.01)。结论:AMPK可能是Ca2+预处理产生心肌保护信号的下游分子。AIM：To evaluate the effect of P5499,an inhibitor of AMPK,on cardioprotection induced by brief calcium depletion preconditioning.METHODS：Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion.Left ventricular pressure（LVP）,left ventricular end-diastolic pressure（LVEDP）,maximum rates of increase and decrease in left ventricular pressure（±dp/dtmax）,heart rate（HR） and coronary flow（CF） were monitored.Left ventricular diastolic pressure（LVDP） and rate pressure product（RPP） were calculated to evaluate myocardial performance.Triphenyltetrazolium chloride staining was used to measure the infarct size of myocardium.RESULTS：In the hearts subjected to global ischemia-reperfusion（I/R group）,levels of LVDP,±dp/dtmax,RPP and CF significantly decreased（P0.01 vs.control group）,and the infarct size was 39.6%±1.49%.Thirty-second perfusion with calcium-free KH solution（CPC group） before I/R reversed all the changes,level of LVEDP was decreased markedly（P0.05 vs.I/R group）,and levels of LVDP,±dp/dtmax,RPP,CF and infarct size were significantly improved（P0.01 vs.I/R group）.P5499 administered before ischemia had no apparent effect on I/R-induced injury but significantly attenuated the cardioprotection of calcium depletion preconditioning（P0.01 vs.CPC group）.CONCLUSION：AMPK may mediate the protective effect of calcium preconditioning against I/R-induced injury.

关 键 词：腺苷酸活化的蛋白激酶 无钙预处理 心肌保护 缺血/再灌注 大鼠 

分 类 号：R542.2[医药卫生—心血管疾病]