川芎嗪对大鼠局部脑缺血后空间学习和记忆的影响

Effect of tetramethylpyrazine on function of spatial learning and memory in rat after focal cerebral ischemia

目的探讨川芎嗪对大鼠局部脑缺血后空间学习记忆能力障碍的作用。方法线栓法制作大鼠大脑中动脉阻塞(MCAO)模型,术后2周内腹腔注射川芎嗪,第15天开始采用Morris水迷宫装置评价大鼠的空间学习记忆能力,脑切片尼氏染色观察皮质和海马的神经元数量变化。结果脑缺血对照组大鼠在定向航行试验和空间探索试验中均表现出明显的空间认知功能的障碍,川芎嗪治疗组大鼠平均逃避潜伏期与缺血对照组比较明显缩短(P<0.01)。在空间探索试验中,川芎嗪治疗组大鼠原平台象限停留时间百分比以及穿过原平台位置次数均大于脑缺血对照组(P<0.01)。在形态学观察中,川芎嗪治疗组大鼠缺血侧顶叶皮质神经元数量明显多于脑缺血对照组(P<0.01),各组动物海马神经元数量上无统计学差异。结论川芎嗪可以明显改善大鼠永久性局部脑缺血后空间学习记忆能力,其机制可能与川芎嗪对神经元的保护作用有关。

Objective To investigate the effects of tetramethylpyrazine on function of spatial learning and memory in rat after focal cerebral ischemia. Methods The focal cerebral ischemic model was established by introducing an intraluminal filament into the left middle cerebral artery of the rat, then tetramethylpyrazine was administered introperitoneally after the operation and afterward once a day for 2 weeks. The spatial learning and memory function was studied by Morris water maze test. Nissl staining technique was conducted for observing the morphology of neurons in cortex and hippocampus. Results The ischemia-control group exhibited seriously spatial learning and memory deficits in both place navigation trail and spatial probe trial. In place navigation trial, the mean values of escape latency of lower-dose, middle-dose and higher-dose tetramethylpyrazine groups were shorter than those of isehemia-control group（P〈0.01）. In spatial probe trial, there were significant difference in the time percentage of spending in the former platform quadrant and frequency of crossing the former platform site between lower, middle and higher-dose tetramethylpyrazine groups and ischemia-control group（P〈0.01）. Compared with ischemia-control group, lower, middle and higher-dose tetramethylpyrazine groups had more neurons of nissl staining in ipsilateral parietal cortex（P〈0.01）. The cell numbers of total neurons of hippocampus had no significant difference between lower, middle and higher-dose tetramethylpyrazine groups and ischemia-control group. Oonclusion Tetramethylpyrazine improves the rat spatial learning and memory ability after focal cerebral isehemia, and the neuroprotective role of the drug in new cortex may be involved in its mechanism.