慢性脑缺血对大鼠认知功能障碍及影响机制研究

Study on cognitive impairment and mechanism causing by chronic cerebral hypoperfusion in rats.

目的观察慢性脑缺血(CCH)过程中大鼠认知功能的变化、前额叶皮层和海马神经元组织学改变以及胆碱能系统改变,探讨慢性脑缺血致大鼠认知障碍的影响机制。方法选取大鼠分组后,应用Morris水迷宫定位航行实验和空间搜索实验观察各组大鼠学习记忆功能变化;苏木精-伊红染色观察前额叶皮层和海马组织学改变;免疫组织化学方法显示前额叶皮层和海马胆碱乙酰转移酶和烟碱型乙酰胆碱受体α4阳性细胞表达。结果①Morris水迷宫测试:a.定位航行实验:各组大鼠逃避潜伏期随天数增加而缩短,逃避潜伏期有差异性;b空间搜索实验:CCH各组大鼠在中环停留时间随低氧时间延长而减少;②与对照组比较,CCH大鼠前额叶皮层和海马变性坏死神经元增多,随着低氧时间延长而加重;③CCH各组大鼠前额叶皮层和海马ChAT阳性表达随低氧时间延长而下降;④CCH各组大鼠前额叶皮层和海马nAChRα4阳性表达随着低氧时间延长而下降。结论慢性脑缺血大鼠认知功能障碍随低氧时间延长呈加重趋势。慢性脑缺血致大鼠认知功能障碍的机制与大鼠前额叶皮层和海马神经元组织学改变和胆碱能系统改变有关。

Objective The model of chronic cerebral hypoperfusion（CCH）in rats is copied,which is used to study the relationship between cognitive impairment causing by CCH and the changes of neuron histology and cholinergic system in prefrontal cortex and hippocampus.Methods Sprague-Dawley rats were randomly averagely divided into four groups.The cognitive function was assessed by the Morris Water Maze.The morphologic changes in prefrontal cortex and hippocampus were observed after stained with HE.The cholin acetyltransferase and nicotinic acetylcholine receptors alpha4 expression in prefrontal cortex and hippocampus were examined by immunohistochemistry.Results ①Morris Water Maze test：a.place navigation：the latency was shortened gradually during the place navigation in all groups and there were significant statistically differences among different days;b.spatial probe：The time rested on the middle ring was gradually reduced in CCH groups while the duration of hypoxia increased.②degeneration or necrosis neurons in prefrontal cortex and hippocampus were significantly increased in CCH rats,and worsen gradually along with the hypoxia.③While the duration of hypoxia increased,the ChAT immunostained cells in prefrontal codex and hippocampus were gradually reduced.④While the duration of hypoxia increased,the nAChRα4 immunostained cells in preftontal conex and hippocampus were gradually reduced.Conclusion The cognitive impairment is worsened gradually in CCH rats along with the process of hypoxia;The mechanism of cognitive impairment in rats causing by CCH correlates with the histopathology changes and cholinergic system changes of prefrontal cortex and hippocampus.