Aβ_(1～40)诱导大鼠海马突触体素和突触数量的变化

Effect of Aβ_(1～40) on expression of synaptophysin and synaptic number of hippocampal neurons in rat after injection of β-amyloid protein 1-40 into hippocampus

目的研究淀粉样β蛋白(β-amyloid protein,Aβ1～40)诱导大鼠海马突触体素和突触数量的变化,以探讨其与阿尔茨海默病发病机制及病理变化的关联性。方法于雄性SD大鼠双侧海马注射Aβ1～40,模拟AD脑内Aβ对神经系统的损害。判定AD模型成功后,取脑行冻切片,采用小鼠抗人重组突触体素单克隆抗体免疫组织化学染色结合积分吸光度分析法检测突触体素免疫阳性产物表达的变化,并应用透射电镜对海马突触进行观察计数。结果假手术组突触体素免疫组化染色海马呈层状结构,突触体素免疫阳性产物密度较高。与假手术组比较,AD模型组突触体素免疫阳性产物密度明显下降,海马CA2突触体素免疫阳性产物的积分吸光度值显著降低(P<0.05)。溶酶体组突触体素免疫组化染色与假手术组相似;电镜观察,假手术组海马神经元树突、轴突较密集,突触小泡多,突触结构清晰、数量多;AD模型组海马神经元突触小泡体积变小、变少,突触结构不完整、数量明显减少(P<0.05),溶酶体组神经元和突触结构与假手术组相似。结论淀粉样β蛋白可诱导大鼠海马突触体素和突触数量表达减少,是阿尔茨海默病发病机制及病理改变之一,是引起学习记忆减退和认知障碍的途径之一。其作用机制尚需进一步探讨。

[Objective] To observe effect of Aβ1-40 on expression of synaptophysin and synaptic number of hippocampal neurons in the rat after injection of β-amyloid protein 1-40 into hippocampus. [Methods] The animal model of AD was established after Aβ1-40 was injected into hippocampus. With the method of immunity histochemical staining coupled with computer image analysis system, observed the expression of synaptophysin in the rat hippocampal neurons. Ultrastructure and synaptic number in the hippocampus were observed by transmission electron microscope. [Results] Synaptophysin immuno：-positive products were widely distributed in neuronal nuclei of hippecampus of sham operation groups rats. Compared with that of sham operation groups, synaptophysin immuno-positive products in the hippocampus CA2 sector neurons were decreased obviously （P 〈0.05） after injection of β-amyloid protein 1-40 into hippocampus. Expression of synaptophysin in the menstruum groups was the same as that in sham operation rats. In hippocampus of Alzheimer＇s disease rats, mitochondria were swollen and deformed, endoplasmic reticulums were dilated, The number of axons and dentrites as well as synapses were decreased obviously （P 〈 0.05）. There was significant difference in synaptic number between Sham operation group and AD group. Synaptic number in the Menstmum groups was the same as that in sham operation rats. [Conclusion] β-amyloid protein may down-regulate the expression of synaptophysin in hippocampus neurons, and the synaptic number in the hippocampus of AD are decreased. They are presumed to be involved in the pathological processes of Alzheimer＇s disease.