EGB1212 post-treatment ameliorates hippocampal CA1 neuronal death and memory impairment induced by transient global cerebral ischemia/reperfusion.
EGB1212 post-treatment ameliorates hippocampal CA1 neuronal death and memory impairment induced by transient global cerebral ischemia/reperfusion.
复制标题
DOI：
10.1142/s0192415x13500894
复制
发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
B. Yin;Hui Liang;Yigang Chen;K. Chu;Li Huang;Ling-na Fang;E. Matro;Wei-jian Jiang;B. Luo
中科院分区：
文献类型：
--
作者：
B. Yin;Hui Liang;Yigang Chen;K. Chu;Li Huang;Ling-na Fang;E. Matro;Wei-jian Jiang;B. Luo
银杏叶提取物作为传统药物已有数百年的历史，在脑缺血/再灌注损伤中具有潜在的临床应用价值。然而，标准化提取物已被证明仅作为预处理具有保护作用，并且主要的作用机制仍不清楚。我们探索了新的提取物EGB 1212的潜力，它符合美国药典（USP）31标准化标准的药物用途，作为一个后处理后，全脑缺血/再灌注（GCI/R）损伤的大鼠模型。预处理组在颈总动脉闭塞前给予EGB 1212 7天（即，缺血20 min）。后处理大鼠接受相同的治疗，但从缺血后2 h开始，持续7 d。GCI/R后7天，各组脑进行海马CA1神经元的H & E染色。剩余大鼠在再灌注后8天开始进行Morris水迷宫和Y-迷宫空间学习和记忆测试。为了评估海马自噬，通过再灌注后12、24或72小时收获的大鼠海马的蛋白质印迹测定轻链（LC）-3-I/LC3-II和Akt/pAkt。EGB1212治疗前和治疗后均改善了神经元存活率和空间学习和记忆功能。预处理有效地降低了LC 3-II水平，而处理后导致pAkt水平显著升高。我们得出结论，EGB1212在GCI/R中的预防和治疗后环境中都发挥了显着的神经保护作用。该提取物显示出巨大的临床应用潜力。
Extracts of Ginkgo biloba have been used in traditional medicines for centuries, and have potential for clinical applications in cerebral ischemia/reperfusion injury. However, standardized extracts have proven protective only as pre-treatments, and the major mechanisms of action remain unclear. We explored the potential of the novel extract EGB1212, which meets the United States Pharmacopeia (USP) 31 standardization criteria for pharmaceutical use, as a post-treatment after global cerebral ischemia/reperfusion (GCI/R) injury in a rat model. The pre-treated group was administered EGB1212 for 7 d prior to common carotid artery occlusion (i.e., ischemia, for 20 min). Post-treated rats received the same but starting 2 h after ischemia and continuing for 7 d. Seven days after GCI/R, brains of each group were processed for H&E staining of hippocampal CA1 neurons. Remaining rats underwent the Morris water maze and Y-maze tests of spatial learning and memory, beginning eight days after reperfusion. To assess hippocampal autophagy, light chain (LC)-3-I/LC3-II and Akt/pAkt were determined via a Western blot of rat hippocampi harvested 12, 24, or 72 h after reperfusion. EGB1212 pre- and post-treatments both improved neuronal survival and spatial learning and memory functions. Pre-treatment effectively reduced LC3-II levels and post-treatment resulted in significantly elevated pAkt levels. We conclude that EGB1212 exerted significant neuroprotection in GCI/R in both preventative and post-treatment settings. This extract shows great potential for clinical applications.