【摘要】 目的　用 β-淀粉样肽 (β- AP)损伤鼠脑胆碱能神经元 ,了解 β- AP对动物认知能力和神经元的损害及 NO在其中的作用。方法　将 β-AP2 5- 3 5定位注射至老化 1 8月龄大鼠脑右侧 Meynert核 ,观察损伤动物学习能力改变 (Y型迷宫法 )。分光光度法检测脑胆碱酯酶 (Ach E)活性 ,并用免疫组化染色法观察鼠脑一氧化氮合酶 (NOS)及凋亡相关蛋白 Bax、Bcl- 2的表达情况。结果　与对照组比较 ,脑损伤老化鼠表现学习能力及脑胆碱酯酶活性显著降低 (均 P<0 .0 1 ) ;NOS2 和 Bax在额叶皮层和海马的表达均升高 ,而 Bcl- 2表达则显著减少 (P均 <0 .0 1 )。结论　 β- AP2 5- 3 5定位损伤脑Meynert核老化大鼠显示胆碱能系统损伤 ,学习能力障碍 ,NOS2 和 Bax表达增加而 Bcl- 2表达降低 ,提示损伤脑有 NO过量生成并诱导发生神经元凋亡损伤。这与 AD病人某些临床和病理特征基本一致。更多还原

【Abstract】 Objectives The rats’ brain cholinergic neurons were lesioned using β-amyloid peptide （β-AP） to observe the damage of rats cognitive ability and brain neurons by β-AP and the role of NO in it. Methods We injected the β-AP25-35 into the brain right Meynert nucleus of eighteen months old rate site-specificly, then measured the learning ability by Y-electric maze, and brain acetylcholinesterase（AchE） activity level by spectrophotography method, the expression of nitrogen oxide synthase-2 （NOS₂） and apoptosis related protein Bax and bcl-2 in rats’ brain were studied using immunohistochemistry method. Results Compared with the control group, the brain damaged rats show that their learning ability is worse, the brain acetylcholinesterase level is lower notably （ P <0.01）. In the frontal cortex and hippocampus the expression of NOS2 and Bax are higher, the expression of bcl-2 is lower significantly than that in control group （ P <0.01）. Conclusions The old rats injured the brain Meynert nucleus by β-AP site-specificly, showed their damage of central cholinergic system and learning disability, the NOS and Bax is over-expressed and bcl-2 is lower expressed. That indicates in damaged brain NO excessive production and induction of neuron apoptosis may exits. The aforesaid characteristic changes are similar to AD patients’ some clinical and pathologic features. So that may be a valuable AD animal model.更多还原