神经生长因子对脑缺血大鼠学习与记忆的影响

Effect of nerve growth factor on the learning and memory of chronic cerebral hypoperfusion rats

目的为了观察神经生长因子(NGF)对脑缺血大鼠学习与记忆的影响和海马内N-甲基-D-天门冬氨酸受体NR2A/B亚zhanghaopeng(NR2A/B)表达的变化。方法本研究将48只成年雄性SD大鼠分为正常组(n=12)、假手术组(n=12)、慢性脑缺血组(n=12)、NGF处理组(n=12)。于造模后开始腹腔注射0.25 ug/100 g NGF,假手术组和慢性脑缺血组腹腔注射等量生理盐水,均1次/d,共21 d。用Morris水迷宫和""Y"迷宫作业测试其空间学习与记忆成绩,再采用Western blot方法分析海马的NR2A、NR2B的表达。结果①Morris水迷宫测试:模型组大鼠寻找平台的潜伏期较假手术组明显延长,NGF处理组大鼠寻找平台的潜伏期较模型组明显缩短;"Y"迷宫测试:模型组大鼠学会躲避电击的正确次数较假手术组明显减少,NGF处理组大鼠学会躲避电击的正确次数较模型组明显增多;②模型组NR2A表达水平较假手术组明显降低,而NR2B明显升高;NGF处理组海马内NR2A表达水平较模型组明显上调,而NR2B明显下调。结论神经生长因子可增强学习与记忆,海马内N-甲基-D-天门冬氨酸(NMDA)受体表达变化可能是影响学习与记忆的机制之一。

Objective To investigate the effect of nerve growth factor（NGF） on the learning and memory of chronic cerebral hypoperfusion rats and the expression changes of N-Methyl-D-aspartic acid（NMDA） receptor subunit NR2A and NR2B in the hippocampus.Methods Forty-eight normal male SD rats were randomly divided into naive group,sham group,chronic cerebral hypoperfusion group and chronic cerebral hypoperfusion treated with NGF group,with 12 in each group.The rats in chronic cerebral hypoperfusion treated with NGF group were injected with 0.25 μg/100g NGF intraperitoneally once each day,while the rats in sham group and chronic cerebral hypoperfusion group were injected with the same dose of saline vehicle.After 3 w of treatment,the interspace learning and memory ability of each group were evaluated by Morris water maze and ＂Y＂ maze.And the expressions of NR2A and NR2B in hippocampus were analyzed with western blot.Results Compared to sham group,the latency to find platform was significantly increased in model group.Compared to model group,the latency to find platform was significantly decreased in chronic cerebral hypoperfusion treated with NGF group.In the test of ＂Y＂ maze,the frequency of successful avoidance of the electric shock was significantly decreased in model group compared to sham group.Compared to model group,the frequency of successful avoidance of the electric shock was significantly increased in the chronic cerebral hypoperfusion treated with NGF group.Compared to sham group,the expression of NMDA receptor subunit NR2A in the hippocampus was significantly down-regulated and the expression of NR2B in the hippocampus was significantly up-regulated.Compared to model group,the expression of NR2A was significantly up-regulated and the expression of NR2B was significantly down-regulated in NGF group.Conclusion These results indicate that NGF might enhance the learning and memory ability of chronic cerebral hypoperfusion rats,and the changes of the expression of NMDA receptors in the hippocampus might be one of the mechanisms that affects the learning and memory ability.