心肌缺血时大鼠离体心脏局部肾素-血管紧张素系统表达的变化

摘要

The anti-myocardial ischemic effect of angiotensin converting enzyme inhibitor (ACEI) and angiotensin Ⅱ receptor antagonist have been substantiated by clinicians and basic researchers, indicating that the local intracardiac renin angiotensin system (RAS) may be activated under such pathological state. Nevertheless, there is no report on the integrated changes of intracardiac RAS, especially chnges of molecular levels after myocardial ischemia. Our study demonstrated that the time and extent of myocardial ischemia might represent a critical factor in the induction of the gene expressions of angiotensinogen, renin, and ACE, leading to the enhanced synthesis of their protein elements. Hence, the AngⅡ contents in cardiac tissues were increased. But such expressions were down-regulated presently during the period of reperfusion, namely, it is only a transient reaction, implying that reperfusion is unlikely to be an activator for the intracardiac RAS. The physiological signification of such diversification needs future clarifying.%临床和基础研究者运用血管紧张素转换酶抑制剂(ACEI)或血管紧张素Ⅱ受体1(AT1)阻断剂都发现它们有抗心肌缺血效应，由此而推断心脏局部肾素-血管紧张素系统(RAS)在此状态下有可能激活，然而，有关心肌缺血后心肌局部RAS成分完整变化的研究特别是分子水平上的研究至今鲜有报道。我们的研究表明，一定时间和一定程度的缺血可以引起心脏局部RAS组成成分血管紧张素原(ANG)、肾素(Renin)和转换酶(ACE)基因表达上调，导致它们相应的蛋白质成分水平上升，最终使其效应物质血管紧张素Ⅱ(AngⅡ)浓度在局部组织中升高。但是，再灌注后心脏局部此表达过程并没有进一步升高，反而有所下降，提示缺血造成的RAS激活是一过性的，比较短暂，再灌注可能不是引起RAS表达增高的因素。心脏局部RAS这种短暂表达究竟有何生理意义尚待进一步的研究予以阐明。