Yabe K, Ishishita H, Tanonaka K, Takeo S
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
J Cardiovasc Pharmacol. 1998 Dec;32(6):962-8. doi: 10.1097/00005344-199812000-00013.
Ischemic preconditioning (I-PC) occurs via activation of protein kinase C (PKC). This study was undertaken to determine whether pharmacologic preconditioning by beta-adrenergic stimulation (beta-PC) is mediated by PKC activation. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. Beta-PC was induced by 0.25 microM isoproterenol pretreatment for 2 min followed by 10-min normoxic perfusion. Beta-PC enhanced the recovery of rate-pressure product of the ischemic/reperfused heart (79.1 +/- 8.4% vs. 12.4 +/- 1.6% of initial for Non-PC group, n = 6) and attenuated the release of creatine kinase during 30-min reperfusion (30.2 +/- 2.2 vs. 59.8 +/- 6.1 nmol/min/g wet wt for Non-PC group, n = 6), similar to an I-PC stimulus of 5-min ischemia and 5-min reperfusion. Treatment with 50 microM polymyxin B, a PKC inhibitor, abolished the cardioprotection of both beta-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induced by both beta-PC and I-PC. The changes in subcellular distribution of PKC-delta suggested its translocation from cytosol to membrane fraction, a marker of PKC activation. These results suggest that the cardioprotection induced by beta-PC, like I-PC, is mediated by PKC activation.
缺血预处理（I-PC）通过蛋白激酶C（PKC）的激活而发生。本研究旨在确定β-肾上腺素能刺激的药物预处理（β-PC）是否由PKC激活介导。将离体大鼠心脏进行40分钟缺血和30分钟再灌注。β-PC通过0.25微摩尔异丙肾上腺素预处理2分钟，随后进行10分钟常氧灌注诱导。β-PC增强了缺血/再灌注心脏的心率-压力乘积恢复（非预处理组为初始值的79.1±8.4%，而初始值为12.4±1.6%，n = 6），并在30分钟再灌注期间减弱了肌酸激酶的释放（非预处理组为30.2±2.2对59.8±6.1纳摩尔/分钟/克湿重，n = 6），类似于5分钟缺血和5分钟再灌注的I-PC刺激。用50微摩尔多粘菌素B（一种PKC抑制剂）处理消除了β-PC和I-PC两者的心脏保护作用。此外，β-PC和I-PC均诱导了PKC亚细胞分布的类似变化。PKC-δ亚细胞分布的变化表明其从胞质溶胶向膜部分的转位，这是PKC激活的一个标志。这些结果表明，β-PC诱导的心脏保护作用与I-PC一样，是由PKC激活介导的。
