摘要
目的:观察Aβ25-35诱导阿尔茨海默病(Alzheimer disease,AD)模型大鼠海马神经营养素3(neuro-trophin-3,NT3)及其受体trkC的表达,并探讨其与AD的关系。方法:30只雄性Wistar大鼠随机分为对照组和模型组。采用立体定向下双侧海马注射A2β5-35建立AD模型,对照组大鼠采用相同方法注射等量生理盐水。2周后,用水迷宫实验测试大鼠学习和记忆功能;然后处死,光镜下观察海马组织结构,免疫组织化学法检测NT3和trkC蛋白的表达。结果:NT3与其受体trkC在两组大鼠海马各区表达变化不同。AD组大鼠海马CA1、CA2、CA3区NT3免疫反应阳性细胞数少于对照组,差异有统计学意义,尤以CA1和CA3区较为明显(P<0.01),而CA4区和hilar区NT3免疫反应阳性细胞数以及海马各区trkC免疫反应阳性细胞数在两组之间差异无统计学意义(P>0.05)。结论:海马神经元NT3的表达含量减少而非其受体trkC的下调与AD模型大鼠学习和记忆功能损害相关,提示补充外源性NT3可有助于减轻A2β5-35的神经元毒性,从而改善其学习和记忆功能。
Objective： To demonstrate the changes in the expression of NT3 and trkC in the hippocampal neurons of Alzheimer disease （AD） rats induced by amyloid β-peptide25-35 （Aβ25-35） and to investigate the mechanism of NT3 and trkC involved in the pathogenesis of AD. Methods：Thirty male Wistar rats were randomly divided into control and model groups. The AD models were established by the injection of amyloid β-peptide25-35 （Aβ25-35 ） into the bilateral hippocampus of rats, while the control rats were subjected to injection of normal saline at the same site. All were tested with the Morris water maze for memory and learning function two weeks after injection. After that, they were killed at the same time. The hippocampal microstructures were observed by an optic microscope. The expressions of NT3 and trkC were detected by an immunohistochemical method. Results： Different expression levels were presented between NT3 and trkC in the different subfields of the hippocampus. The number of NT3 imunoreactive neurons within the hippocampal subfields CA1, CA2 and CA3 in the model group was obviously reduced compared with the control group （P 〈 0.01）, while no difference was found in the CA4 and hilar subfields between the two groups （P 〉 0.05）. No difference in the number of trkC imunoreactive neurons in each hippocampal subfield was produced between the two groups （ P 〉 0.05）. Conclusion： The decrease of the expression of NT3 but not the down-regulation of its receptor＇s in the hippocampus is related to learning and memory dysfunction of AD rats, suggesting an exogenous NT3-supply may counteract the neurotoxieity of β amyloid protein.
出处
《山东大学学报（医学版）》
CAS
北大核心
2007年第3期290-294,298,共6页
Journal of Shandong University:Health Sciences
