Angiotensin converting enzyme 2/Ang-(1-7)/mas axis protects brain from ischemic injury with a tendency of age-dependence.
Angiotensin converting enzyme 2/Ang-(1-7)/mas axis protects brain from ischemic injury with a tendency of age-dependence.
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DOI：
10.1111/cns.12233
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发表时间：
2014-05
影响因子：
5.5
通讯作者：
Chen YF
中科院分区：
文献类型：
--
作者：
Zheng JL;Li GZ;Chen SZ;Wang JJ;Olson JE;Xia HJ;Lazartigues E;Zhu YL;Chen YF
血管紧张素转换酶2（ACE 2）/Ang-（1-7）/Mas受体通路是肾素-血管紧张素系统的重要组成部分，在缺血性卒中中发挥有益作用。本研究探讨ACE 2/Ang-（1-7）/Mas通路是否对脑缺血损伤具有保护作用以及这种作用是否受年龄的影响。我们使用了三个月和八个月的转基因小鼠与神经过度表达ACE 2（SA）和他们的年龄匹配的非转基因（NT）的控制。在大脑中动脉闭塞（MCAO）后测定神经功能缺损和缺血性每搏输出量。在脑切片的氧和葡萄糖剥夺（OGD）实验中，测量Mas受体激动剂（Ang 1 -7）或拮抗剂（A779）对组织肿胀、Nox 2/Nox 4表达、活性氧（ROS）产生和细胞死亡的影响。(1)SA小鼠大脑中动脉闭塞引起的缺血性损伤和神经功能缺损减轻，尤其是在8月龄动物中：（2）SA小鼠OGD引起的组织肿胀和细胞死亡减少，在8月龄小鼠中观察到更大的减少;（3）Ang-（1-7）和A779对OGD诱导的反应有相反的作用，其作用与Nox 2/Nox 4表达和ROS产生的变化有关。血管紧张素转换酶2/Ang-（1-7）/Mas轴通过Nox/ROS信号通路保护脑免受缺血损伤，在老年动物中效果更好。
The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor pathway is an important component of the renin–angiotensin system and has been suggested to exert beneficial effects in ischemic stroke. This study explored whether the ACE2/Ang-(1-7)/Mas pathway has a protective effect on cerebral ischemic injury and whether this effect is affected by age. We used three-month and eight-month transgenic mice with neural over-expression of ACE2 (SA) and their age-matched non-transgenic (NT) controls. Neurological deficits and ischemic stroke volume were determined following middle cerebral artery occlusion (MCAO). In oxygen and glucose deprivation (OGD) experiments on brain slices, the effects of the Mas receptor agonist (Ang1-7) or antagonist (A779) on tissue swelling, Nox2/Nox4 expression reactive oxygen species (ROS) production and cell death were measured. (1) Middle cerebral artery occlusion -induced ischemic injury and neurological deficit were reduced in SA mice, especially in eight-month animals; (2) OGD-induced tissue swelling and cell death were decreased in SA mice with a greater reduction seen in eight-month mice; (3) Ang-(1–7) and A779 had opposite effects on OGD-induced responses, which correlated with changes in Nox2/Nox4 expression and ROS production. Angiotensin converting enzyme 2/Ang-(1-7)/Mas axis protects brain from ischemic injury via the Nox/ROS signaling pathway, with a greater effect in older animals.