Changes in responses to ischemic attack associated with ageing : analyses by a new mouse model which shows a syndrome resembling ageing

背景老年急性心肌梗死患者预后较差。但其病理生理机制尚不清楚，尚待解决。最近发展了一种新的小鼠模型(Kloth小鼠)，它表现出类似衰老的症状。目的我们研究Klotho小鼠和野生小鼠在对缺血/再灌流攻击的破坏性和保护性反应方面是否存在差异。方法麻醉和插管后，Klotho小鼠(n=8)和野生小鼠(n=8)阻断左冠状动脉20分钟，然后再灌流60分钟。测定再灌注区心肌髓过氧化物酶活性、超氧化物歧化酶活性、热休克蛋白和总胆红素含量。结果再灌注区的总胆红素含量明显高于野生组，提示再灌注区存在氧化应激反应。我们发现Klotho鼠再灌注性心律失常的发生率明显高于野鼠。在对缺血/再灌流攻击反应的破坏因子方面，两组髓过氧化物酶活性无显著差异。而Klotho鼠再灌注区作为保护因子的SOD活性和热休克蛋白活性均显著低于野鼠(P&lt；0.05)。结论Klotho鼠再灌注损伤明显大于野鼠，这可能与老年急性心肌梗死患者预后不良有关。这可能是由于在对缺血/再灌流攻击的反应中，保护性因子如SOD活性和热休克蛋白产生的减少而不是破坏性因子的增加所致。

<Background> The prognosis of elder patients with acute myocardial infarction is poor. However, its pathophysiological mechanism is not clear and remains to be solved. A new mouse model (the kloth mouse), which shows a syndrome resembling ageing, has recently developed.<Objective> We investigated whether there are differences in destructive and protective responses to ischemic/reperfused attack between the klotho and wild mouse.<Methods> After anesthesia and intubation, we occluded the left coronary artery in the klotho mice (n=8) and wild mice (n=8) for 20 minutes and then reperfused for 60 minutes. We measured the myeloperoxidase activity, SOD activity, heat shock protein and TBARS in reperfused myocardium.<Results> The TBARS in reperfused area, which should indicate oxidative stress after reperfusion, was significantly greater in the klotho mice as compared with that in the wild mice. We found that the ocurrcnce of reperfusion arrhythmia in the klotho mice was significantly greater than in wild mice. With regard to the destructive factor in response to ischemic/reperfused attack, there was no significant difference in myeloperoxidase activity between the two groups. In contrast, both SOD activity and heat shock protein as protective factors in responses to ischemic/reperfused attack were significantly depressed in reperfused area of the klotho mice as compared with the wild mice (P<0.05).<Conclusion> We found that the reperfusion injury in the klotho mice was significantly greater than that in the wild mice, which may be consistent with the poor prognosis in elder patients with acute myocardial infarction. This may result from the depression of the protective factors such as reduction in SOD activity and heat shock protein production rather than the increase in the destructive factors in responses to ischemic/reperfused attack.