Wang Zhi-fei, Tang Li-li, Yan Han, Wang Yu-jun, Tang Xi-can
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
Pharmacol Biochem Behav. 2006 Apr;83(4):603-11. doi: 10.1016/j.pbb.2006.03.027. Epub 2006 May 9.
This study is to investigate the effects of huperzine A on memory deficits, neuronal damage and neurotrophic factors production after transient cerebral ischemia and reperfusion in mice, as well as the potential downstream signaling pathway. Bilateral common carotid occlusion (BCCAo) combined with systemic hypotension induced severe memory deficits in a water maze task and neuronal degeneration in cerebral cortex and hippocampus in mice. Oral administration of huperzine A (0.2 mg/kg, once per day, started 2 days before surgery and lasted for 7 days after surgery) markedly attenuated the memory deficits and neuronal damage. Meanwhile, huperzine A significantly increased the mRNA and protein levels of NGF, BDNF and TGF-beta(1), and potentiated phosphorylation of MAPK/ERK 1/2 in both cerebral cortex and hippocampus compared with transient cerebral ischemia and reperfusion group. This study provides evidence for the protective effects of huperzine A against transient cerebral ischemia and reperfusion in mice, and suggests potentially important roles that neurotrophic factors might play in these effects. It also indicates that the MAPK/ERK pathway might be involved in the in vivo neurotrophic effects of huperzine A against transient cerebral ischemia and reperfusion.
本研究旨在探讨石杉碱甲对小鼠短暂性脑缺血再灌注后记忆缺陷、神经元损伤及神经营养因子产生的影响，以及潜在的下游信号通路。双侧颈总动脉闭塞（BCCAo）联合全身低血压可导致小鼠在水迷宫任务中出现严重的记忆缺陷以及大脑皮层和海马体中的神经元变性。口服石杉碱甲（0.2mg/kg，每天一次，在手术前2天开始，持续至手术后7天）可显著减轻记忆缺陷和神经元损伤。同时，与短暂性脑缺血再灌注组相比，石杉碱甲显著提高了大脑皮层和海马体中NGF、BDNF和TGF-β(1)的mRNA和蛋白水平，并增强了MAPK/ERK 1/2的磷酸化。本研究为石杉碱甲对小鼠短暂性脑缺血再灌注的保护作用提供了证据，并提示神经营养因子在这些作用中可能发挥的潜在重要作用。它还表明MAPK/ERK通路可能参与了石杉碱甲对小鼠短暂性脑缺血再灌注的体内神经营养作用。
