Imagawa J i, Baxter G F, Yellon D M
The Hatter Institute for Cardiovascular Studies, University College London Hospital and Medical School, Grafton Way, London, WC1E 6DB, UK.
J Mol Cell Cardiol. 1997 Jul;29(7):1885-93. doi: 10.1006/jmcc.1997.0428.
We have previously reported a delayed or "second window of protection" against infarction 24-72 h after ischemic preconditioning in the rabbit. This phenomenon has also been associated with the protein kinase C signalling pathway. In the present study, we expanded our investigation to ascertain whether protein tyrosine kinase was in any way associated with this phenomenon in the rabbit heart. We found that 48 h after ischemic preconditioning with 4x5 min coronary occlusions the percentage of myocardium infarcting within the risk zone following a 30-min coronary occlusion and 120-min reperfusion (I/R) was reduced from 39. 6+/-3.3% to 18.0+/-3.7% (P<0.01). However, an i.v. bolus administration of genistein (5 mg/kg), a tyrosine kinase inhibitor, 5 min before ischemic preconditioning stimulus, abolished this protection (I/R=39.0+/-3.4%). Genistein per se had no significant effect on infarction 48 h later. Risk zone volume after coronary ligation was not significantly different between intervention groups. There were no differences in hemodynamic parameters between groups throughout the experimental period. We conclude that the second window of protection, 48 h after preconditioning, is mediated by tyrosine kinase activation in the rabbit heart.
我们之前报道过，家兔缺血预处理后24至72小时会出现延迟性或“第二保护窗”，可预防梗死。这种现象也与蛋白激酶C信号通路有关。在本研究中，我们扩大了调查范围，以确定蛋白酪氨酸激酶是否以任何方式与家兔心脏的这一现象有关。我们发现，在进行4次5分钟冠状动脉闭塞的缺血预处理后48小时，30分钟冠状动脉闭塞和120分钟再灌注（I/R）后危险区内梗死心肌的百分比从39.6±3.3%降至18.0±3.7%（P<0.01）。然而，在缺血预处理刺激前5分钟静脉推注酪氨酸激酶抑制剂染料木黄酮（5毫克/千克）可消除这种保护作用（I/R=39.0±3.4%）。染料木黄酮本身在48小时后对梗死无显著影响。各干预组冠状动脉结扎后的危险区体积无显著差异。在整个实验期间，各组的血流动力学参数无差异。我们得出结论，预处理后48小时的第二保护窗是由家兔心脏中的酪氨酸激酶激活介导的。
