摘要 阿尔茨海默病（Alzheimer’s disease，AD）是一种进行性发展的致死性神经退行性疾病。近年来的研究发现AD可能是一种慢性中枢神经炎症反应疾病，这引导我们探索新型化合物对AD相关神经炎症调控作用及其机制。在经过一系列新型化合物筛选以后，我们发现化合物M4在LPS或Aβ诱导的小胶质细胞中，对IL-1β、IL-6和TNF-α炎症因子的产生有明显的抑制作用，并呈现剂量和时间依赖性。机制研究发现，M4减弱细胞核因子-κB（NF-κB）的转录活性，该作用与ReLA / p65的磷酸化和核位移的反向调节有关。而且，LPS诱导的有丝分裂原活化蛋白激酶（MAPKs）的活化，如细胞外信号调节激酶（ERK）和p38蛋白，分别在不同程度上被M4改变。因此，M4可以通过调节小胶质细胞内一系列细胞内信号通路抑制小胶质细胞活化和炎症因子的产生，且该作用有可能是通过MAPK和NF-κB调控p65磷酸化和核转位对NF-κB相关炎症因子的转录和炎症反应的发生产生影响。89294

   Alzheimer's disease (AD) is a progressive development of lethal neurodegenerative disease。 Recent studies have shown that AD may be a chronic central nervous system inflammatory response disease, which leads us to explore the new compounds on AD-related neuroinflammatory regulation and its mechanism。 After screening for a series of novel compounds, we found that compound M4 significantly inhibited the production of IL-1β, IL-6 and TNF-α inflammatory factors in LPS or Aβ-induced microglia and showed a dose And time dependence。 Mechanisms have found that M4 attenuates the transcriptional activity of nuclear factor-κB (NF-κB), which is related to the reverse regulation of phosphorylation and nuclear translocation of ReLA / p65。 Moreover, LPS-induced activation of mitogen-activated protein kinase (MAPKs), such as extracellular signal-regulated kinases (ERK) and p38 proteins, were altered to varying degrees by M4, respectively。 Therefore, M4 can regulate microglia cells through a series of intracellular signaling pathway to inhibit microglia activation and inflammatory factors, and this effect may be through the MAPK and NF-κB regulation p65 phosphorylation and nuclear translocation of NF-κB-related inflammatory factors and the occurrence of inflammatory response。

毕业论文关键词：神经炎症；小胶质细胞；阿尔茨海默病 

Keyword: Neuroinflammation；Microglia：Alzheimer's disease 

目    录

1。引言 4

2材料与方法 5

2。1试剂 5

2。2细胞培养 6

2。3细胞活力源Y于U优I尔O论P文W网wwW.yOueRw.com 原文+QQ75201-8766 分析 6

2。4 RNA分离和实时定量PCR 6

2。5 细胞因子的表达 6

2。6 免疫印迹分析 6

2。7 免疫荧光染色和共聚焦显微镜 7

2。8 Morris水迷宫 7

2。8。1实验动物及分组 7

2。8。2动物实验 7

2。9统计分析 7

3结果 8

3。1初筛 8

3。2M4的抗炎作用 9

3。2。1 M4对BV2细胞活力无影响 9

3。2。2 M4降低LPS诱导的小胶质细胞促炎基因的表达