稳态强磁场下细胞凋亡的多基因调控机制研究

The strong static magnetic field (SMF) is one of the important extreme conditions of the frontiers in modern science. With the development of the science and technology of SMF, the interaction of SMF and the biological organism and the involved mechanism(s) have caused great concerns and become one of the substantially scientific issues. Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in an extensive variety of diseases such as cancer. Based on the facilities located in the High Magnetic Field Laboratory of the Chinese Academy of Sciences, the present project was focused on the apoptotic process under SMF in caenorhabditis elegans to clarify the relationship between the apotosis and the exposure time and the magnetic field intensity, the mechanism(s) of apotosis induced by SMF which involved the key regulation genes and the signal pathway. Our data will provide novel evidence on the response of the biological organisms to SMF and the exposure standard of SMF, which will be helpful in the application of SMF.

强磁场是现代前沿科学研究重要极端条件之一。随着强磁场科学与技术的发展，强磁场对生物有机体的作用及相关机制研究已成为人们所关注的重要科学问题之一。细胞凋亡是在所有多细胞生物中起关键作用的基本生命过程，具有重要的生物学意义和临床意义。本项目拟依托中国科学院强磁场科学中心大科学装置，利用秀丽隐杆线虫及其基因缺陷型品系，系统研究稳态强磁场下细胞凋亡与磁场强度、暴露时间及暴露方式之间的量变规律，解析稳态强磁场下细胞凋亡的基因调控机制，揭示稳态强磁场下细胞凋亡程序启动的关键信号分子及信号传导通路，为阐明生物有机体对稳态强磁场的响应及生物安全边界标准的建立提供新的实验基础，并为稳态强磁场在生物医学领域的应用提供重要依据。

随着稳态强磁场(SMF)科学和技术的迅速发展，其生物效应及健康风险评估已引起人们广泛关注，但由于装置的限制，相关研究目前尚处起步阶段。依托合肥稳态强磁场装置，本项目利用遗传背景清晰的模式生物—秀丽隐杆线虫（C. elegans）,从个体层面研究不同强度稳态强磁场对其生殖腺细胞凋亡的影响及关键信号通路。研究结果显示，1）线虫卵暴露于8.5T SMF可显著降低其平均寿命，并呈时间依赖关系，而5T SMF无此现象；2）尽管SMF对产卵率无影响，但8.5T SMF可引发发育速度和阶段异常；3）在成虫线虫中，8.5T SMF通过凋亡核心信号通路介导能诱导生殖腺细胞凋亡水平显著上升，而自由基清除剂可起到保护作用，并且相比野生型，氧化损伤敏感品系对SMF响应程度更高，其超氧化物歧化酶sod-3的蛋白和mRNA表达显著升高； 4）利用daf-2和daf-16的缺陷品系，揭示稳态强磁场引起的线虫发育异常与insulin-like信号通路密切相关。上述研究结果为阐释SMF引发生殖及发育异常的机制提供了新的实验依据。