自噬对重离子引发的神经细胞死亡或凋亡的调控作用

项目名称： 自噬对重离子引发的神经细胞死亡或凋亡的调控作用

项目编号： No.31200636

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 马宏

作者单位： 北京理工大学

项目金额： 23万元

中文摘要： 虽然重离子在太空辐射射线中所占比重较小，但因其能量高、危害大、防护难，成为空间辐射损伤效应研究的重点和难点。现有研究显示辐射可诱发自噬等非细胞凋亡性的细胞死亡，并且自噬和凋亡存在着广泛的联系，但是重离子辐射后自噬对凋亡的调控作用还不明确，分子机制的实验证据还不充分。本课题以前期神经胶质瘤细胞辐射耐受机理研究中的自噬的保护作用为出发点，拟通过体内及体外两个层面探寻自噬对辐射后细胞死亡或凋亡的调控作用，重点研究重离子辐射后神经细胞死亡的生命进程；同时，确定1-2个影响重离子辐射损伤效应的关键因子，探索运用分子生物学手段干预其表达、改变细胞辐射敏感性，以增强细胞抵抗空间辐射的自我防护能力的可行性。本研究成果将可能为空间辐射损伤生物防护策略提供有力的理论补充。

中文关键词： 自噬；凋亡；辐照；耐受性；治疗

英文摘要： Exposure to radiation is one of the main concerns for space exploration by humans. The nature and the frequency of accelerated heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response. Previous cytogenetic data undoubtedly revealed that space radiation exposure produced significant damage in neuron cells, such as serious membrane lesions and multiple chromatin breaks. Some reports indicated that capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. However, our knowledge of the basic molecular mechanisms of cell death induced by heavy ions specific to low-dose, to repeated doses and to adaptive response is still poor. It is possible that some of the characteristic changes of cell death may represent a delayed effect of chromatin misrepair in brain. Thus, in our studies, we want to know whether radiation can induce autophagy of neuron cell or glial cell in vitro or in vivo, which would play an important role in cell death and regulate the cell apoptosis mediated by irradiation. Furthermore, it is important to find the key factors of heavy ions radiation effect and to explore the use of molecular biology means to intervene in the expression of these genes, which might change the cell sen

英文关键词： autophage；apoptosis；irradiation；resistance；therapy