Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model
Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model
复制标题
黄体酮通过减少大鼠实验性蛛网膜下腔出血模型中的细胞凋亡和氧化应激来减轻急性脑损伤
DOI：
10.1016/j.neulet.2015.06.023
复制
发表时间：
2015-07-23
影响因子：
2.5
通讯作者：
Dai, Yuying
中科院分区：
文献类型：
--
作者：
Cai, Jing;Cao, Shenglong;Dai, Yuying
本研究旨在探讨黄体酮对蛛网膜下腔出血（SAH）后急性脑损伤的治疗作用。雄性 Sprague-Dawley 大鼠（n = 72）通过血管内穿孔诱导蛛网膜下腔出血。 SAH 后 1、6 和 12 小时给大鼠施用黄体酮（8 mg/kg 或 16 mg/kg）。实验 SAM 后 24 小时测定死亡率、神经功能缺损、细胞凋亡、凋亡标记物的表达、丙二醛 (MDA) 水平和超氧化物歧化酶 (SOD) 活性。黄体酮治疗的 SAH 大鼠死亡率、细胞凋亡和 caspase-3 表达均降低，神经功能得到改善。此外，研究表明，黄体酮显着降低了 Bax/Bcl-2 的比率，并减弱了线粒体中细胞色素 c 的释放。 SAH 后，黄体酮还可通过提高 SOD 活性并降低 MDA 含量来诱导抗氧化作用。此外，观察了黄体酮治疗的剂量反应关系，高剂量黄体酮增强了神经保护作用。黄体酮治疗可以通过抑制细胞凋亡和减少氧化应激造成的损伤来减轻 SAH 后的急性脑损伤。其抗凋亡作用的机制与线粒体途径有关。这些结果表明黄体酮具有成为治疗SAH后急性脑损伤的新型治疗剂的潜力。 (C) 2015 Elsevier Ireland Ltd. 保留所有权利。
This study aimed to investigate the therapeutic effect of progesterone on acute brain injury after subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced in male Sprague-Dawley rats (n = 72) by endovascular perforation. Progesterone (8 mg/kg or 16 mg/kg) was administered to rats at 1, 6, and 12 h after SAH. Mortality, neurologic deficits, cell apoptosis, expression of apoptotic markers, the level of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were assayed at 24 h after experimental SAM. Mortality, cell apoptosis and the expression of caspase-3 were decreased, and improved neurological function was observed in the progesterone-treated SAH rats. Further, exploration demonstrated that progesterone significantly reduced the ratio of Bax/Bcl-2 and attenuated the release of cytochrome c from mitochondria. Progesterone also induced anti-oxidative effects by elevating the activity of SOD and decreasing MDA content after SAH. Furthermore, dose-response relationships for progesterone treatment were observed, and high doses of progesterone enhanced the neuroprotective effects. Progesterone treatment could alleviate acute brain injury after SAH by inhibiting cell apoptosis and decreasing damage due to oxidative stress. The mechanism involved in the anti-apoptotic effect was related to the mitochondrial pathway. These results indicate that progesterone possesses the potential to be a novel therapeutic agent for the treatment of acute brain injury after SAH. (C) 2015 Elsevier Ireland Ltd. All rights reserved.