机械敏感TRP离子通道在剪切力致神经元损伤中的调控作用及在弥漫性轴索损伤法医学鉴定中的应用探索

项目名称： 机械敏感TRP离子通道在剪切力致神经元损伤中的调控作用及在弥漫性轴索损伤法医学鉴定中的应用探索

项目编号： No.81471821

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 董红梅

作者单位： 华中科技大学

项目金额： 70万元

中文摘要： 弥漫性轴索损伤（DAI）是死因鉴定的难点，其发生是由于外伤在脑组织内产生剪切力，引起病理生理变化，最终致轴索广泛断裂。Ca2+超载被认为是中心环节，期间包含着机械力与Ca2+超载之间力学-生化信号转导。机械敏感离子通道是力信号传导最常见途径之一，其中瞬时受体电位通道(TRP)与机械力传导和Ca2+通透均有关，前期研究通过PCR芯片筛选出多个TRP通道基因在DAI中表达增加，但受外力作用TRP通道如何引起神经元及轴浆内Ca2+超载以及在DAI中的作用尚不明确。本项目拟用剪切力加载神经元建立体外DAI模型，通过电生理、形态学及荧光检测等技术来探讨TRP离子通道在剪切力致神经元损伤中的作用及可能机制，另外在该模型观察筛选出的TRP通道蛋白的表达，并进一步在尸检脑组织研究这些通道蛋白与DAI病变的关系。本项目通过DAI发病力学-生化信号转导机制的探讨以期为该病法医鉴定及临床诊治的进展提供研究基础。

中文关键词： 剪切力；神经元；弥漫性轴索损伤；机械敏感离子通道；瞬时受体电位通道

英文摘要： Diffuse axonal injury (DAI) is induced by shear force in brain injury, which results in a series of pathophysiological changes and eventually leads to the axonal disruption. It has been thought that Ca2+ overloding plays a central role in the pathophysiological process of DAI, during which Ca2+ overloading resulted from the mechanical signal transduction into biochemistry signal is included. Mechanosensitive channel is one of the most common pathways in mechnical signal transduction, in which transient receptor potential (TRP) channels are related with mechanotransduction and Ca2+ influx.The preliminary study indicated that the expression of several TRP mRNAs was increased by PCR chip.But the mechanism of Ca2+ overloding through TRP mechanosensitive channel in axons after external force is unclear, and its role in the pathogenesis of DAI is uncertain too. In the present study, the neurons under shear forces will be constructed to imitate DAI model in vitro. The experiment skills of electro-physiology,morphology and flueorescence etc will be used to observe the effects of TRP mechanosensitive channel on neurons under shear force.On the other hand, the TRP proteins, which were screened by PCR chip in DAI rat, were verified in neurons induced by shear force. The relationship between the expression of mechanosensitive channel TRP proteins and DAI in the brain tissue by autopsy will be observed too. This study would provide the research foundation for the development of diagnosis, treatment and forensic identification of DAI.

英文关键词： Shear force;Neuron;Diffuse axonal injury;Mechanosensitive ion channel;Transient receptor potential channels