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
柳景华,丁燕生,孙璐,范煜东,张英川
摘要(Abstract):
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。
关键词(KeyWords): 缺血预处理,心肌;动作电位;多黏菌素B
基金项目(Foundation):
作者(Author): 柳景华,丁燕生,孙璐,范煜东,张英川
参考文献(References):
- [1]Churchill EN,Mochly-Rosen D.The roles of PKCdelta and epsi-lon isoenzymes in the regulation of myocardial ischaemia/reperfu-sion injury.Biochem Soc Trans,2007,35:1040-1042.
- [2]柳景华,任自文,汪丽蕙,等.缺血预适应对兔心脏电生理参数的影响.中国介入性心脏病学杂志,2000,8:48-51.
- [3]Cohen MV,Liu GS,Downey JM.Preconditioning causes im-proved wall motion as well as smaller infarcts after transient coro-nary occlusion in rabbits.Circulation,1991,84:341-345.
- [4]Hund TJ,Lerner DL,Yamada KA,et al.Protein kinase Cepsi-lon mediates salutary effects on electrical coupling induced by is-chemic preconditioning.Heart Rhythm,2007,4:1183-1193.
- [5]Shiki K,Hearse DJ.Preconditioning of ischemic myocardium:reperfusion-induced arrhythmias.Am J Physiol,1987,253:H1470-1476.
- [6]Ovize M,Aupetit J,Rioufol G,et al.Preconditioning reduce in-farct size but accelerates time to ventricular fibrillation in ische-mic pig heart.Am J Physiol,1995,269:H72-76.
- [7]Franz MR.Long-term recording of monophasic action potentialsfrom human endocardium.Am J Cardiol,1983,51:1629-1632.
- [8]Kuno A,Critz SD,Cui L,et al.Protein kinase C protects pre-conditioned rabbit hearts by increasing sensitivity of adenosineA2b-dependent signaling during early reperfusion.J Mol CellCardiol.2007,43:262-271.