Involvement of angiotensin-(1-7) in the neuroprotection of captopril against focal cerebral ischemia
Involvement of angiotensin-(1-7) in the neuroprotection of captopril against focal cerebral ischemia
复制标题
血管紧张素-(1-7)参与卡托普利对局灶性脑缺血的神经保护作用
DOI：
10.1016/j.neulet.2018.09.024
复制
发表时间：
2018
影响因子：
2.5
通讯作者：
Zhang Ying Dong
中科院分区：
文献类型：
--
作者：
Tao Meng Xing;Xue Xiao;Gao Li;Lu Jun Ling;Zhou Jun Shan;Jiang Teng;Zhang Ying Dong
越来越多的证据表明，脑血管紧张素转换酶（ACE）/血管紧张素II/血管紧张素II I型受体轴被激活，从而有助于缺血性脑卒中时的神经元损伤。相反，使用中枢活性ACE抑制剂卡托普利抑制该轴被证明在具有局灶性脑缺血的啮齿动物中具有神经保护作用。有趣的是，卡托普利能够增加外周器官中的血管紧张素-（1-7）[Ang-（1-7）]水平。Ang-（1-7）作为脑内替代性肾素-血管紧张素系统轴的主要成分，通过MAS 1受体依赖性方式对局灶性脑缺血具有保护作用。基于这些证据，我们推测Ang-（1-7）可能参与了缺血性卒中时卡托普利的神经保护作用。在这项研究中，我们评估了这一假设使用大鼠模型局灶性脑缺血。我们发现，在局灶性脑缺血大鼠脑ACE 2活性和血管紧张素-（1-7）水平显着升高后，卡托普利治疗。更重要的是，我们发现卡托普利提供的神经保护作用可被Ang-（1-7）受体MAS 1的拮抗剂A-779部分逆转，表明Ang-（1-7）参与了卡托普利的神经保护作用。这些发现揭示了卡托普利对抗局灶性脑缺血的新机制，并进一步表明，除了其抗高血压作用外，卡托普利可能具有预防和治疗中风的实际临床用途。
Accumulating evidence suggests that brain angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type I receptor axis is activated and thus contributes to the neuronal injury during ischemic stroke. Conversely, inhibition of this axis using centrally active ACE inhibitor captopril was proven neuroprotective in rodents with focal cerebral ischemia. Interestingly, captopril was able to increase angiotensin-(1–7) [Ang-(1–7)] levels in the peripheral organs. As the main component of the alternative renin-angiotensin system axis in the brain, Ang-(1–7) was revealed to protect against focal cerebral ischemia via a MAS1 receptor-dependent manner. Based on this evidence, we hypothesized that Ang-(1–7) might contribute to the neuroprotection of captopril during ischemic stroke. In this study, we evaluated this hypothesis using a rat model of focal cerebral ischemia. We revealed that brain ACE2 activity and Ang-(1–7) levels were significantly elevated following captopril treatment in rats with focal cerebral ischemia. More importantly, we showed that the neuroprotection provided by captopril was partially reversed by A-779, an antagonist for Ang-(1–7) receptor MAS1, indicating that Ang-(1–7) was involved in the neuroprotection of captopril. These findings have uncovered new mechanisms by which captopril protects against focal cerebral ischemia and further suggest that captopril may have practical clinical use for stroke prevention and treatment in addition to its antihypertensive effect.