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

<Background>老年急性心肌梗死患者预后差。然而，其病理生理机制尚不清楚，仍有待解决。最近开发出一种新的小鼠模型（kloth小鼠），它表现出类似衰老的综合征。<Objective>我们研究了klotho和野生小鼠之间对缺血/再灌注攻击的破坏性和保护性反应是否存在差异。<Methods>麻醉和插管后，我们阻断klotho小鼠（n=8）和野生小鼠（n=8）的左冠状动脉20分钟，然后再灌注60分钟。测定再灌注心肌组织中髓过氧化物酶活性、超氧化物歧化酶活性、热休克蛋白和TBARS。<Results>与野生小鼠相比，klotho小鼠再灌注区的TBARS显著更大，这应该表明再灌注后的氧化应激。我们发现klotho小鼠再灌注心律失常的发生率明显高于野生小鼠。关于缺血/再灌注发作时的破坏因素，两组间髓过氧化物酶活性无显著差异。而klotho小鼠再灌注区SOD活性和热休克蛋白作为缺血/再灌注保护因子均明显低于野生型小鼠（P&lt;0.05）。<Conclusion>我们发现klotho小鼠的再灌注损伤明显大于野生小鼠，这可能与老年急性心肌梗死患者预后差相一致。这可能是由于缺血再灌注时保护性因素如SOD活性降低和热休克蛋白产生减少所致，而不是由于缺血再灌注时破坏性因素增多所致。

<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.