RKIP在工频磁场暴露对阿尔茨海默症发生影响中的作用及机制研究

项目名称： RKIP在工频磁场暴露对阿尔茨海默症发生影响中的作用及机制研究

项目编号： No.51307181

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 电工技术

项目作者： 刘肖

作者单位： 中国人民解放军军事医学科学院

项目金额： 25万元

中文摘要： 流行病学调查显示，工频磁场（MF）可能增加阿尔茨海默症（AD）的发病风险，然MF与AD关系的实验研究尚未见报道。研究表明，RKIP参与AD的病理过程。我们研究发现，RKIP与MF对AD发生的影响密切相关。基于RKIP对海马Ach及凋亡调控的重要意义，我们推测RKIP在MF对AD的影响中可能发挥重要作用。本项目拟以RKIP为切入点，深入探讨MF对AD发生的影响及机制。首先，建立MF联合AD动物模型，研究MF对AD大鼠认知功能、海马结构及AD标志物的影响，并检测海马Ach合成与代谢、RKIP磷酸化及其凋亡信号通路以及蛋白相互作用改变；然后,通过MF联合Aβ诱导的原代海马神经元和PC12神经细胞凋亡模型，分别应用HCNP、抑制剂、RKIP过表达、RNA干涉等，研究RKIP介导的Ach及凋亡调控在MF对AD影响中的作用。这将进一步揭示MF与AD的关系，阐明RKIP相关分子机制，并为防治提供新思路。

中文关键词： 工频磁场；阿尔茨海默病；RKIP；凋亡；

英文摘要： It has been reported that power frequency magnetic field (MF) exposure may promote the genesis of Alzeimer's disease (AD) in epidemiology investigation.However,the experimental report about the relationship between MF and AD is still unknown. RKIP has been indicated to be participated in the pathological process of AD. Our study found that RKIP was well related with the influence of MF on AD genesis. Based on the importance of the regulation of Ach and apoptosis by RKIP, we postulate that RKIP is critical for the influence of MF on AD. Taking RKIP as the starting point, this study will deeply investigated the influence of MF on AD genesis and its mechanisms. Firstly, the animal model of MF combined with AD will be established, then the influences of MF on cognitive function, hippocampus stucture and bio-markers of AD in AD rats will be explored. Moreover, the changes of Ach synthesis and metabolism,the phosphorylation of RKIP and its apoptotic-related signalling pathways, and protein interaction will be detected. Secondly, the apoptotic cell models of primary hippocampus neurons and PC12 neural cells induced by MF combined with Aβ will be used. HCNP, inhibitor, RKIP overexpression and RNA interference et al will be applied to investigate the role of regulation of Ach and apoptosis mediated by RKIP in the influe

英文关键词： power frequency magnetic field；Alzeimer's disease；RKIP；apoptosis；