模拟微重力环境下TLR9分子在碳离子辐射损伤防护中的作用及机理研究

项目名称： 模拟微重力环境下TLR9分子在碳离子辐射损伤防护中的作用及机理研究

项目编号： No.81501623

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张超

作者单位： 中国人民解放军联勤保障部队第九四〇医院

项目金额： 18万元

中文摘要： 载人航天任务已成为航天计划优先发展的目标，但宇航员在进入太空后，空间辐射成为威胁其健康不可忽视的因素，使用药物以提高机体对辐射的抵抗能力成为空间辐射防护的一种有效方法。近年来，TLR9与辐射防护的关系引起了放射医学界的高度重视，当TLR9与激动剂CpG-ODN特异性结合后会募集MyD88，一方面通过TRAF3活化IKKε，另一方面通过IRAK-4、IKAK-1、TRAF6和TAK1，活化IKKα和IKKβ，最终促使IκBα磷酸化降解，活化NF-κB。前期研究显示TLR9激动剂CpG-ODN能通过激活NF-κB以减轻γ射线对小鼠骨髓和小肠的损伤，提高存活率。在本次课题中我们将在模拟空间微重力环境下，使用碳离子照射模拟空间辐射，通过正性和负性调控技术，探讨TLR9是否在微重力环境下对以重离子损伤为主要效应的空间辐射损伤也发挥显著的防护作用，并阐明其机理，为航天辐射防护剂的研制提供新理论和新思路。

中文关键词： 空间辐射；重离子；模拟微重力；TLR9；航天辐射防护剂

英文摘要： Currently, Manned Space missions have became top priority to space program, and many astronauts were sent to space. However, the astronauts would be affected by space radiation, which was the important damage factor that seriously threatens their health. So, space radioprotector was essential to enhance the body radio-resistance ability. Recently, the relationship between TLR9 and radiation protection are going to get a lot of attention. Some data showed that TLR9 recognized CpG-ODN and activates MyD88, On the one hand, MyD88 recruits TRAF3, and activates IKKε; On the other hand MyD88 recruits IRAK4, IRAK1, TRAF6 and TAK1 complex, activates IKKα and IKKβ. IKKs causes IκBα destroy by the proteasome pathway and then directly activated NF-κB. Previous study indicated CpG-ODN/TLR9 reduced bone marrow and small intestine damage and enhanced mice survival after γ-rays by activating NF-κB and inhibiting cell apoptosis. In this study, we will investigate the role of TLR9 in the damage-induced by carbon ions beam radiation under the stimulated microgravity environment by activating or knockout TLR9, and clarify the possible mechanism. We believed that this study would provide a new strategy and idea for development of space radioprotector.

英文关键词： Space radiation;Heavy ions;Stimulated microgravity ;TLR9;Space radiprotector