多黏菌素B阻断蛋白激酶C活化后的缺血心肌保护作用

Inhibition of activated protein kinase C mediated ischemic myocardium protection by polymyxin B sulfate

目的通过硫酸多黏菌素B抑制蛋白激酶C（PKC）活化,探讨PKC活化在缺血心肌保护中的作用。方法将健康家兔30只随机分为缺血组（IS组,10只）、缺血预适应组（IPC组,10只）和硫酸多黏菌素B组（PMB组,10只）,按照文献方法建立缺血和预适应模型。用多导电生理记录仪同步记录左室压力数据、曲线及单向动作电位（MAP）图形。结果各实验组不改变缺血兔缺血和再灌注期心率,IPC组心率和收缩压乘积明显高于其他组。PKC活化对左室收缩功能有明显保护作用,但对左室舒张功能保护作用不明显。IS组、PMB组MAP振幅（MAPA）、除极最大速率（dv/dt max）在缺血期5~20min明显缩短;IPC组变化不明显,而PMB可以抵消IPC保护作用,导致心肌细胞传导速度延缓和复极离散度增加。PMB并不能增加电交替、室性早搏和心室颤动的发生率。结论PKC活化可以降低心肌坏死、改善左室收缩功能,但并不能降低电交替、室性早搏和心室颤动的发生,表明IPC抗心肌缺血坏死和抗心律失常分属不同的机制,PKC活化并不参与抗心律失常作用。

Objective To identify the role of protein kinase C （PKC） activation in ischemic myocardium proctection and its effect after inhibition by polymyxin B sulfate. Methods We randomly divided 30 rabbits into ischemic （IS） group, ischemic preconditioning （IPC） group and polymyxin B sulfate （PMB） group. According to the method reported in previous literature, we simultaneously recorded ECG, pressure curve and monophasic action potential （MAP） throughout the ischemia and reperfusion perocess. Results The rabbit heart rates were not changed significantly during the ischemic or reperfusion period. The products of heart rate multiplying systolic pressure were significantly higher in IPC group compared with the other two groups （ P 〈 0. 05 ）. The activation of PKC protected the systolic function of left ventricle but did not have the same effects on the diastolic function. There was no apparent shortening of MAP amplitude （MAPA）, dv/dt max during the 5 - 20 min of ischemic period in IPC group compared with the other 2 groups. PMB might abolish the protective effect of IPC, reduced the conduction velocity of myocardial cells and relatively increased the repolarization dispersion. PKC deactivated by PMB could not increase the rates of electrical alternans, ventricular premature beats and ventricular fibrillation. Conclusion The activation of PKC might reduce the myocardial necrosis, improve the systolic function of left ventricle, but could not reduce the electrical alternans, ventricular premature beats and ventricular fibrillation. The anti-ischemic and anti-arrhythmic effects of PKC might not generate through the same pathways. PKC activation may not take part in anti-arrhythmia.