普仑司特对东莨菪碱诱导的小鼠学习记忆损害的影响

Effects of Pranlukast on Scopolamine-induced Memory Impairment in Mice

关键词:  普仑司特  东莨菪碱  学习记忆  乙酰胆碱  乙酰胆碱酯酶

Key words:  pranlukast  scopolamine  learning and memory  acetylcholine  acetylcholinesterase

摘要:

目的 研究普仑司特对东莨菪碱诱导小鼠学习记忆损害的影响及其作用机制。方法 采用连续腹腔注射东莨菪碱(0.8 mg·kg^-1·d^-1)诱导小鼠学习记忆损害模型，灌胃给予普仑司特(0.3，0.6，1.2 mg·kg^-1·d^-1)，14 d后用Morris水迷宫和Y迷宫实验评价学习记忆功能，并测定脑内乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)水平。结果 普仑司特(0.3~1.2 mg·kg^-1·d^-1)能显著缩短小鼠在隐藏平台实验中寻找平台的潜伏期，增加空间探索实验中在原平台所在象限的停留时间和穿越原平台所在位置的次数，增加Y迷宫测试中正确反应次数。普仑司特还能显著增加小鼠脑组织海马区和皮层区Ach含量，并降低AchE活性。结论 普仑司特通过降低脑内AchE活性，提高Ach含量，改善东莨菪碱诱导的小鼠学习记忆损害。

Abstract:

OBJECTIVE To investigate the effects of pranlukast on memory impairment induced by scopolamine in mice and its underlying mechanisms. METHODS Pranlukast(0.3, 0.6, 1.2 mg·kg^-1·d^-1) was orally administered 0.5 h after intraperitoneal injection with scopolamine (0.8 mg·kg^-1·d^-1) for consecutive 14 days. Memory function was evaluated by Morris water maze and Y maze tests. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine (Ach) and acetylcholinesterase(AchE) in the hippocampus and cortex. RESULTS Treatment with pranlukast(0.3-1.2 mg·kg^-1·d^-1) significantly decreased the escape latency in hidden platform test and increased the time spent in the platform quadrant and the number of platform location crossings in the spatial probe test, and increased the correct number in Y maze test. Pranlukast also significantly increased Ach level and decreased AchE activity in the hippocampus and cortex. CONCLUSION Pranlukast may improve scopolamine-induced memory impairment through elevation of brain Ach levels resulting from inhibition of AchE activity in mice.