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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 investigate the effect of AMPK inhibitor P5499 on myocardial protection induced by transient calcium-free preconditioning. Methods: The heart of healthy SD male rats were perfused with Langendorff in vitro. The changes of coronary flow (CF), left ventricular pressure (LVP), left ventricular end diastolic pressure (LVEDP) (dp / dtmax) and heart rate (HR). The left ventricular systolic pressure (LVDP) and heart rate-pressure product (RPP) were calculated to evaluate the changes of cardiac function. After reperfusion, changes in myocardial infarction (MI) area were evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Results: After ischemia / reperfusion (I / R), cardiac function was significantly reduced, CF significantly decreased (P <0.01), and the area ratio of MI was (39.6 ± 1.49)%. After a brief period of calcium-free preconditioning (CPC), LVEDP was significantly decreased (P <0.05), CF, LVDP, ± dp / dtmax and RPP were significantly improved (P <0.01). MI area was significantly reduced (P <0.01). P5499 given before ischemia had no significant effect on cardiac function, CF and MI area, but it could significantly reverse the myocardial protective effect of CPC (P <0.01). Conclusion: AMPK may be a downstream molecule of Ca2 + preconditioning to generate myocardial protection signal.