MAPK信号通路对电磁脉冲致血脑屏障通透性增加的调控作用及始动因素研究

项目名称： MAPK信号通路对电磁脉冲致血脑屏障通透性增加的调控作用及始动因素研究

项目编号： No.60871068

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 郭国祯

作者单位： 中国人民解放军第四军医大学

项目金额： 35万元

中文摘要： 中枢神经系统是电磁辐射最主要的靶器官，电磁辐射引起中枢神经系统形态和功能的改变与血脑屏障通透性的增加密切相关。我们的研究表明：电磁辐射所致ZO-1等紧密连接相关蛋白基因的下调是导致血脑屏障通透性增加的主要原因，但是导致紧密连接蛋白下调的信号通路及原初作用过程尚不清楚。本项目以血脑屏障体外模型为研究对象，采用免疫电镜、荧光染色、分子抑制剂阻断、RT-PCR和蛋白杂交等方法，探讨MAPK信号转导通路调节BBB通透性的分子机理。为阐明EMP引起BBB通透性改变的MAPK信号转导通路的原初作用机制，采用膜片钳和跨内皮电阻检测等方法验证EMP是否通过直接的物理作用引起MAPK信号转导通路的改变，从生物化学角度出发，利用自由基及其清除剂，验证EMP是否通过间接化学作用激活MAPK信号通路。该研究可为深入理解电磁辐射的作用机制及预防和治疗电磁辐射对中枢神经系统损伤提供一定的理论和实验基础。

中文关键词： 电磁脉冲；血脑屏障；MAPK；原初作用

英文摘要： Central nervour system (CNS)is the main target organ of electromagnetic radiation, and the changes of morphology and function in CNS induced by electromagnetic radiation has the tight relationship with the increasing of Blood-brain- barrier(BBB) permeability .Our prior studies showed: It's the main reason to cause BBB permeability increasing that some tight junction protein such as ZO-1 down regulation induced by electromagnetic radiation,but we aren't clear about the signal pathway and original contribution of tight junction protein down regulation up to now.In present study,we will use BBB in vitro model to study,and use immune electron microscope, fluorescence staining, molecule inhibitor blocking,RT-PCR and Western blotting et al, to investigate the molecular mechanism of MAPK signal pathway regulating BBB permeability. To elucidate the initial mechanism of BBB permeability change through MAPK signal pathway induced by EMP,we will apply patch clamp and Transepithelial electrical resistance（TER） measure to proof whether the change of MAPK signal pathway induced by EMP through direct physical effect or not. At the biochemistry view,we will investigate whether the change of MAPK signal pathway induced by EMP through indirect chemical effect or not using some free radical scavenger.Present study will provide some theoretical and experimental foundation for thorough understanding the mechansim of electromagnetic radiation and prevention and therapeutics CNS damage induced by electromagentic radiation.

英文关键词： electromagnetic pulse；blood-brainbarrier；MAPK；initial effect