Valtchanova-Matchouganska A, Gondwe M, Nadar A
Tara Hospital, The Morose Centre, Johannesburg, South Africa.
Cardiovasc J S Afr. 2005 Mar-Apr;16(2):118-23.
The involvement of C-reactive protein (CRP) in early (acute) and delayed ischaemic (IPC) and pharmacological (chemical) (CPC) preconditioning in an in vivo model of rat myocardial infarction is presented. Acute IPC was produced by three 5-min occlusion (ischaemia) periods interspersed with 5 min reperfusion, followed by 30-min occlusion of the left coronary artery and 2 h reperfusion injury. Acute CPC was produced by a Kappa-opioid receptor agonist U50488H (5 mg/kg) applied i.v. 15 min before 30-min ischaemia/2-h reperfusion. Delayed preconditioning was produced by 30-min ischaemia/2-h reperfusion, induced 24 h after either ischaemic or pharmacological preconditioning. The myocardial ischaemia/reperfusion injury was evaluated on the basis of total and cardiac creatine kinase isoenzyme activity, functional recovery of the heart (ECG), infarct size (% IS/RA) and mortality at the end of the experiments. The results obtained showed that: . The Kappa-opioid receptor agonist U50488H mimics both the acute and delayed IPC in the above experimental protocol. .Both acute IPC and CPC produce effects by opening of the KATP channels (the effects were blocked by nonspecific ATP-sensitive K channel blocker glybenclamide), and via activation of protein kinase C (a selective protein kinase C inhibitor chelerythrine blocked the effects). .C-reactive protein was significantly elevated by 54% in non-preconditioned acute ischaemia/reperfusion injury. The elevation was more pronounced (82% increase) 24 h after non-preconditioned ischaemia/ reperfusion injury. It reflected very well the increase in cardiac isoenzymes, infarct size and mortality of the rats, and can be used as a marker of the severity of myocardial injury in this model. . The increase of CRP was prevented by both IPC and CPC in early, and especially in late preconditioning. This shows the involvement of CRP, not only as a marker, but as a causative factor in cardiac ischaemic/reperfusion injury.
In addition to the established involvement of adenosine, bradykinin, opioid and other receptors, a suppression of myocardial CRP/complement production might be involved in the biological mechanism of preconditioning. This could be a promising perspective in clinical interventions against ischaemia/reperfusion injuries of the heart.
本文介绍了C反应蛋白（CRP）在大鼠心肌梗死体内模型的早期（急性）和延迟缺血预处理（IPC）以及药理（化学）预处理（CPC）中的作用。急性IPC通过三个5分钟的闭塞（缺血）期并穿插5分钟的再灌注产生，随后左冠状动脉闭塞30分钟并进行2小时的再灌注损伤。急性CPC通过在30分钟缺血/2小时再灌注前15分钟静脉注射κ-阿片受体激动剂U50488H（5mg/kg）产生。延迟预处理通过在缺血或药理预处理后24小时诱导的30分钟缺血/2小时再灌注产生。根据总肌酸激酶同工酶活性和心肌肌酸激酶同工酶活性、心脏功能恢复（心电图）、梗死面积（%IS/RA）以及实验结束时的死亡率评估心肌缺血/再灌注损伤。获得的结果表明：.κ-阿片受体激动剂U50488H在上述实验方案中模拟了急性和延迟IPC。.急性IPC和CPC均通过开放KATP通道产生作用（这些作用被非特异性ATP敏感性钾通道阻滞剂格列本脲阻断），并通过激活蛋白激酶C产生作用（选择性蛋白激酶C抑制剂白屈菜红碱阻断了这些作用）。.在未预处理的急性缺血/再灌注损伤中，C反应蛋白显著升高54%。在未预处理的缺血/再灌注损伤后24小时，升高更为明显（增加82%）。它很好地反映了大鼠心肌同工酶、梗死面积和死亡率的增加，并且可以用作该模型中心肌损伤严重程度的标志物。.在早期，尤其是晚期预处理中，IPC和CPC均能阻止CRP的升高。这表明CRP不仅作为标志物，而且作为心脏缺血/再灌注损伤的致病因素参与其中。
除了已确定的腺苷、缓激肽、阿片类和其他受体的参与外，心肌CRP/补体产生的抑制可能参与预处理的生物学机制。这可能是针对心脏缺血/再灌注损伤的临床干预的一个有前景的方向。
