Wang L M, Han Y F, Tang X C
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 200031, Shanghai, People's Republic of China.
Eur J Pharmacol. 2000 Jun 9;398(1):65-72. doi: 10.1016/s0014-2999(00)00291-0.
The effects of (-)-huperzine A, a promising therapeutic agent for Alzheimer's disease, on learning behavior and on alterations of the cholinergic system, the oxygen free radicals and energy metabolites induced by permanent bilateral ligation of the common carotid arteries were investigated in rats. Daily oral administration of huperzine A produced a significant improvement of the deficit in the learning of the water maze task, beginning 28 days after ischemia, correlating to about 33-40% inhibition of acetylcholinesterase activity in cortex and hippocampus. Huperzine A significantly restored the decrease in choline acetyltransferase activity in hippocampus and significantly reduced the increases in superoxide dismutase, lipid peroxide, lactate and glucose to their normal levels. The present findings demonstrate that the improvement by huperzine A of the cognitive dysfunction in the late phase in chronically hypoperfused rats is due to its effects, not only on the cholinergic system, but also on the oxygen free radical system and energy metabolism. Our results strongly suggest that huperzine A has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow.
石杉碱甲是一种很有前景的治疗阿尔茨海默病的药物，本研究在大鼠中考察了其对双侧颈总动脉永久性结扎诱导的学习行为、胆碱能系统改变、氧自由基及能量代谢产物的影响。自缺血后28天起，每日口服石杉碱甲可显著改善水迷宫任务学习缺陷，这与皮层和海马中乙酰胆碱酯酶活性约33%-40%的抑制相关。石杉碱甲可显著恢复海马中胆碱乙酰转移酶活性的降低，并使超氧化物歧化酶、脂质过氧化物、乳酸和葡萄糖的升高显著降低至正常水平。本研究结果表明，石杉碱甲对长期灌注不足大鼠晚期认知功能障碍的改善，不仅归因于其对胆碱能系统的作用，还归因于其对氧自由基系统和能量代谢的作用。我们的结果强烈提示，石杉碱甲对治疗由胆碱能功能障碍和/或脑血流量减少引起的痴呆具有治疗潜力。
