Aβ在小胶质细胞中的内吞、转运和降解的研究

发布时间：2018-04-22 21:28

本文选题：小胶质细胞 + 吞噬　；参考：《厦门大学》2014年硕士论文

【摘要】：阿尔茨海默症是一种主要的导致痴呆的老年疾病,其临床特征为细胞外的淀粉样沉淀和胞内的神经元缠结。淀粉样沉淀的主要组成成分是淀粉样蛋白(β-amyloid, Aβ)。大脑内的Aβ的产生和降解的平衡被扰乱是现在比较公认的阿尔茨海默症的发病机制。Aβ分为可溶性和不可溶性两种形式,研究显示可溶性的Ap比不可溶的Aβ的毒性更大,Ap的清除速度即使有很缓慢的降低也会导致Aβ的聚集,进而产生Aβ的沉积。小胶质细胞是中枢神经系统中的一种巨噬细胞,之前的研究显示小胶质细胞可以通过液相的大胞饮途径,在Ap的内吞和降解中发挥重要的作用,但其具体机制还不是很清楚。在本研究中我们发现与N2a神经胶质瘤细胞相比,BV-2小胶质细胞具有很强的内吞Ap的能力,不仅能较快速并且能内吞更多的Ap；我们接着发现小胶质细胞有多重内吞Ap的方式；随着Aβ被吞进小胶质细胞后,能很快到达溶酶体进而被降解；我们通过ELISA方法量化两种细胞降解Ap的能力,发现小胶质细胞能降解更多的Ap。我们的研究还发现Ap在小胶质细胞中的转运有两条途径：再循环途径和降解途径,而且在小胶质细胞中Aβ主要是经降解途径降解,都说明小胶质细胞有很强的降解Aβ的能力。我们的研究揭示了小胶质细胞在淀粉样蛋白的降解中发挥的作用,表明了小胶质细胞在阿尔茨海默症的病程发展中有重要的作用,这些研究为深入揭示阿尔茨海默症的发病机制提供了新的信息。
[Abstract]:Alzheimer's disease is a major senile disease leading to dementia, its clinical characteristics are extracellular amyloid precipitation and intracellular neuronal tangles. The main component of amyloid precipitation is amyloid (A 尾 -amyloid). The disruption of the balance between the production and degradation of A 尾 in the brain is now more commonly recognized as the pathogenesis of Alzheimer's disease. A 尾 is divided into soluble and insoluble forms. The results show that soluble Ap is more toxic than insoluble A 尾. The scavenging rate of Ap can lead to the accumulation of A 尾 and the deposition of A 尾, even if it decreases slowly. Microglia are a kind of macrophages in the central nervous system. Previous studies have shown that microglia can play an important role in the endocytosis and degradation of AP through the liquid phase macrocytic pathway, but its specific mechanism is not very clear. In this study, we found that BV-2 microglia cells had a strong ability to endocytosis of AP, not only faster but also more Apps than N2a glioma cells, and then we found the way of multiple endocytosis of Ap in microglia cells. When A 尾 was swallowed into microglia, the lysosome was quickly reached and then degraded. We quantified the ability of two kinds of cells to degrade AP by ELISA method, and found that microglia could degrade more App. We also found that there are two pathways for the transport of AP in microglia: recirculation pathway and degradation pathway, and A 尾 in microglia is mainly degraded by degradation pathway, indicating that microglia have a strong ability to degrade A 尾. Our study revealed the role of microglia in amyloid degradation, suggesting that microglia play an important role in the progression of Alzheimer's disease. These studies provide new insights into the pathogenesis of Alzheimer's disease.
【学位授予单位】：厦门大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.16

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