循环血辐射敏感microRNA调控淋巴细胞辐射损伤的机理研究

淋巴细胞是免疫系统最重要的细胞成分之一，淋巴细胞辐射损伤效应的研究对于辐射安全和防护具有重要意义。循环血microRNA（miRNA）是近年来的研究热点，已有研究表明多种循环血miRNA对辐射具有响应，但是其对机体淋巴细胞辐射损伤的影响还不清楚。我们的前期研究以小鼠为模型，筛选得到了一组对重离子束和X射线都具有较强敏感性的循环血miRNA，并发现辐照后上调循环血中miR-342的水平能抑制辐射导致的淋巴细胞数量减少。以此为切入点，本项目拟利用重离子和X射线照射小鼠，通过尾静脉注射agomiRNA干扰辐照后循环血miR-342的水平，进一步研究对各类淋巴细胞及细胞因子的影响；此外，以淋巴母细胞作为细胞模型，通过miRNA过表达和沉默技术，对miR-342调控的靶基因和参与的分子通路进行研究，揭示其发挥保护作用的分子机制，为未来开发以循环血miRNA为靶点的辐射防护新方法提供思路。

Lymphocytes are one of the key cellular components of immune system. The study on radiation damage effect of lymphocytes is crucial for radiation safety and protection. Circulating microRNA (miRNA) is a hot topic in recent years. Previous studies showed that radiation can induced differential expression of miRNAs in blood. However, the effects of radiosensitive circulating miRNA on lymphocytes is still unclear. In our former studies, we found a set of blood miRNAs is strongly sensitive to heavy ion and X-ray irradiation in mice, and up-regulation of miR-342 in blood after irradiation could alleviate radiation induced decrease of lymphocytes. In this project, the levels of miR-342 will be interfered in blood of mice exposed to heavy ions and X-rays by tail injection of agomiRNA, and the impacts on lymphocytes and cytokines will be further detected. In addition, we will investigate the target gene and relevant pathway of miR-342 by miRNA overexpression and RNAi in lymphoblast model to uncover the mechanism of miR-342 in protecting lymphocytes after irradiation. These results will provide new sight for making circulating miRNAs as target of protection after exposure.