Glycine confers neuroprotection through PTEN/AKT' signal pathway in experimental intracerebral hemorrhage
Glycine confers neuroprotection through PTEN/AKT' signal pathway in experimental intracerebral hemorrhage
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DOI：
10.1016/j.bbrc.2018.04.171
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发表时间：
2018
影响因子：
3.1
通讯作者：
Wan Qi
中科院分区：
文献类型：
--
作者：
Zhao Dan;Chen Juan;Zhang Ya;Liao Hua-Bao;Zhang Zhi-Feng;Zhuang Yang;Pan Meng-Xian;Tang Jun-Chun;Liu Rui;Lei Yang;Wang Shu;Qin Xing-Ping;Feng Yu-Gong;Chen Yun;Wan Qi
甘氨酸已被证明通过各种机制防止缺血性中风。10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）拮抗Akt依赖性细胞存活，与神经元损伤有关。然而，甘氨酸在脑出血（ICH）中是否具有神经保护特性尚不清楚。本研究旨在探讨甘氨酸对大鼠脑出血的保护作用。对成年雄性Sprague-Dawley（SD）大鼠进行左纹状体自体血液输注。ICH动物在ICH后1 h接受甘氨酸（0.2-3 mg/kg，icv），在甘氨酸给药前0.5 h预先注射或不注射Akt抑制剂IV（100 μM，2 μl，icv）。我们的研究结果表明，在血肿周围区的PTEN表达上调，在早期阶段，ICH。然而，甘氨酸治疗降低了血肿周围区域的PTEN蛋白水平，并增加了AKT的磷酸化水平（p-AKT）。甘氨酸能明显减少脑出血后神经元的死亡，减轻伊文思蓝渗漏和脑水肿。此外，血肿体积减少，神经行为结局改善。然而，Akt抑制剂IV消除了甘氨酸在ICH后的神经保护作用。总之，我们的研究结果首次证明了甘氨酸对ICH大鼠的保护作用，并表明甘氨酸的神经保护作用是通过PTEN/Akt信号通路介导的。
Glycine has been shown to protect against ischemic stroke through various mechanisms. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) which antagonize Akt-dependent cell survival has been linked to neuronal damage. However, whether glycine has a neuroprotective property in intracerebral hemorrhage (ICH) was unknown. This study aimed to determine the protective effect of glycine in rats ICH. Adult male Sprague-Dawley (SD) rats were subjected to left striatum infusion of autologous blood. ICH animals received glycine (0.2–3 mg/kg, icv) at 1 h after ICH with or without pre-injection of Akt Inhibitor IV (100 μM, 2 μl, icv) 0.5 h prior to glycine treatment. Our results showed that in the perihematomal area PTEN was up-regulated in the early stage after ICH. However, glycine treatment decreased PTEN protein level and increased the phosphorylation level of AKT (p-AKT) in the perihematomal area. With the administration of glycine, neuronal death was significantly reduced and Evans blue leakage was alleviated as well as the brain edema after ICH. Moreover, hematoma volume was decreased and neurobehavioral outcome was improved. Nevertheless, Akt Inhibitor IV abolished the neuroprotective effects of glycine after ICH. Together, our findings demonstrate, for the first time, the protective role of glycine on ICH rats, and suggest that the neuroprotective effect of glycine was mediated through PTEN/Akt signal pathway.