Meynert核损伤老化鼠脑组化改变及神经元凋亡机制研究

Study on the Mechanism of Brain Histochemistry Change and Neurons Apoptosis of Old Rats With Meynert Nucleus Damaged

目的 用兴奋性神经毒素N -甲基 -D -天冬氨酸 (NMDA)损伤大鼠脑胆碱能神经元 ,研究NMDA损伤对认知能力和神经元凋亡的影响及NO在其中的作用。方法 用NMDA定位注射损伤老化大鼠脑右侧Meynert核。测定损伤动物学习能力改变 (Y型迷宫法 ) ,检测脑胆碱酯酶活性 (分光光度法 ) ,并用免疫组化染色法观察动物脑皮层及海马一氧化氮合酶 (NOS)及凋亡相关蛋白Bax、Bcl- 2表达阳性神经元的变化情况。结果 与对照组比较 ,经NMDA损伤后老化大鼠显示学习能力及脑胆碱酯酶活性显著降低。 (P <0 0 1)NOS和Bax在额叶皮层和海马的表达阳性神经元数量均显著升高 ,而Bcl- 2阳性神经元数量则显著减少。 (P <0 0 1)。结论 兴奋性毒素NMDA定位损伤脑Meynert核后 ,老化大鼠显示胆碱能系统损伤 ,学习能力障碍。损伤脑NOS酶表达增加 ,提示有NO过量生成。Bax过表达而Bcl- 2表达降低 ,显示脑中诱导发生神经元凋亡。

Objective To observe the effects of excitatory neurotoxin,NMDA(N-methyl-D-asparate) damage on congnitive ability and neurons apoptosis,and to explore the role of NO in the process.Methods NMDA solution(10μg/μl) was injected orientationally into the brain right Meynert nucleus of old rats,then the learning ability of the damaged rats was measured by Y-electric maze,and by spectropho to graphy method,observed the brain acetylcholinesterase(AchE) activity,The changes of the expression of NOS-2(nitric oxide synthase-2) and positive neurons of apoptosis related protein Bax and Bcl-2 in the rats brain cortex and hippocampus were determined by using immunohistochemistry staining techiuque.Results As compared with the control group,the old rats group damaged by NMDA showed that their learning ability was worse , the brain acetylcholinesterase activity was lower notably. (P<0 01).In the brain amount of expression positive neurons of NOS-2 and Bax was much more, but the expression of Bcl-2 was less than that in control group significantly.(P<0 01).Conclusions After impairing the right Meynert nucleus with injection of NMDA site-specificly, the old rats show that their damage of the central cholinergic system and the learning disability, and the expression of NOS in damaged brain is increased which indicats the excessive production of NO. The excessive expression of Bax ,but lower expression of Bcl-2 suggests that the neuron apoptosis were induced in brain. Therefore that the characteristic changes of the model rats are similar to some clinical and pathologic features in AD patients.