Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, PR China.
Neuropeptides. 2013 Oct;47(5):289-95. doi: 10.1016/j.npep.2013.09.002. Epub 2013 Sep 18.
There is now unequivocal evidence that the angiotensin-converting enzyme 2(ACE2)-Ang-(1-7)-Mas axis is a key component of the renin-angiotensin system (RAS) cascade, which is closely correlated with ischemic insult occurrence. Our previous studies demonstrated that the Ang-(1-7), was an active member of the brain RAS. However, the ACE2-Ang-(1-7)-Mas axis expression after cerebral ischemic injury are currently unclear. In the present study, we investigated the time course of ACE2-Ang-(1-7) and Mas receptor expression in the acute stage of cerebral ischemic stroke. The content of Ang-(1-7) in ischemic tissues and blood serum was measured by specific EIA kits. Real-time PCR and western blot were used to determine messenger RNA (mRNA) and protein levels of the ACE2 and Mas. The cerebral ischemic lesion resulted in a significant increase of regional cerebral and circulating Ang-(1-7) at 6-48 h compared with sham operation group following focal ischemic stroke (12h: 7.276±0.320 ng/ml vs. 2.466±0.410 ng/ml, serum; 1.024±0.056 ng/mg vs. 0.499±0.032, brain) (P<0.05). Both ACE2 and Mas expression were markedly enhanced compared to the control in the ischemic tissues (P<0.05). Mas immunopositive neurons were also seen stronger expression in the ischemic cortex (19.167±2.858 vs. 7.833±2.483) (P<0.05). The evidence collected in our present study will indicate that, ACE2-Ang-(1-7)-Mas axis are upregulated after acute ischemic stroke and would play a pivotal role in the regulation of acute neuron injury in ischemic cerebrovascular diseases.
现在已经有明确的证据表明,血管紧张素转换酶 2(ACE2)-血管紧张素(1-7)-Mas 轴是肾素-血管紧张素系统(RAS)级联反应的一个关键组成部分,与缺血性损伤的发生密切相关。我们之前的研究表明,血管紧张素(1-7)是大脑 RAS 的一个活跃成员。然而,目前尚不清楚脑缺血损伤后 ACE2-Ang-(1-7)-Mas 轴的表达情况。在本研究中,我们研究了急性脑缺血性卒中时 ACE2-Ang-(1-7)和 Mas 受体表达的时间进程。采用特异性 EIA 试剂盒测定缺血组织和血清中 Ang-(1-7)的含量。实时 PCR 和 Western blot 用于测定 ACE2 和 Mas 的信使 RNA(mRNA)和蛋白水平。与假手术组相比,局灶性缺血性卒中后 6-48 小时,缺血组织和循环中的 Ang-(1-7)含量显著增加(12h:7.276±0.320ng/ml 比 2.466±0.410ng/ml,血清;1.024±0.056ng/mg 比 0.499±0.032,脑)(P<0.05)。与对照组相比,缺血组织中 ACE2 和 Mas 的表达明显增强(P<0.05)。在缺血皮质中也观察到 Mas 免疫阳性神经元的表达增强(19.167±2.858 比 7.833±2.483)(P<0.05)。我们目前的研究结果表明,急性缺血性卒中后 ACE2-Ang-(1-7)-Mas 轴被上调,并在调节缺血性脑血管病中的急性神经元损伤中发挥关键作用。