局部照射是核事故和放疗普遍存在的受辐射方式，敏感组织损伤是辐射危害的内因。本项目拟在我们前期大量细胞水平研究积累的基础上，从个体水平上研究辐射远端效应以及外泌体在其中的作用。以X射线定位照射小鼠右肺后1天至6个月，检测小鼠左肺、小肠、骨髓、血液等组织的病理变化和其中干细胞的损伤，通过外泌体抑制剂确定外泌体在辐射远端效应中的作用；收集辐照前后小鼠外周血中外泌体，分析其中蛋白和miRNA分子的变化，检测辐射诱导的外泌体在体内的分布及其对骨髓、小肠及它们所含干细胞的损伤；基于辐射前后外泌体中显著差异蛋白和miRNA，建立相应的过表达载体和抑制基因并将之转染肺上皮细胞，研究受辐射肺细胞所释放外泌体对骨髓干细胞、小肠隐窝细胞等的损伤；通过构建miRNA分子模拟物和动物实验验证，获知几种与辐射远端效应密切相关的miRNAs，探索其分子靶点，有望发现新的辐射信号分子，为放射损伤救治与防护提高新的策略。

Local body irradiation is popular in radiation accident and radiotherapy, and the radiation harmful effect is mainly depended on the damage situation of radiosensitive tissues. Based on our previous plenty works on cell radiation responses, this program will study the mechanisms of radiation induced abscopal effect (RIAE) by locally irradiating the right lung of mouse with X-rays and investigate the roles of exosomes in this effect by treating the mouse with an inhibitor of exosome release before and after irradiation. After 1d to 6 months of irradiation, the cell damage and pathological alters in the left lung, small intestine and its stem cells , marrow and mesenchymal stem cells (MSC), and blood will be measured. The exosomes in the blood before and after irradiation will be collected to assay the containing proteins and miRNAs and the changes will be analyzed. After being marked with a stable fluorescence dye, the exosomes will be injected into mouse though caudal vein and its distribution in the body will be detected. In addition, the cell and tissue responses to the external exosomes will be measured. Accordingly to the obvious changes of the proteins and miRNAs in the exosomes before and after irradiation, their over-expression plasmids and siRNAs will be constructed and transferred into a pulmonary epithelial cell MLE-12. After irradiation, the exosomes from irradiated MLE-12 cells are collected and send to MSC and small intestinal crypt epithelial cell IEC-6 in order to identify the functional proteins and miRNAs. The molecule targets of miRNAs will be studied as well. Moreover, the agomir and antagomir of a few selected miRNAs will be injected into mouse to further verify the roles of miRNAs in RIAE. The new signal factors of RIAE can be expected from this study, which could provide new treatment strategies for radiation injury.