新型靶向配体CL429防治辐射损伤的作用及机制

重度电离辐射损伤的防护和治疗是世界难题，亟待解决。我们筛选出一种对辐射损伤具有明确防护和治疗作用、高效低毒的新型靶向配体CL429。与现有辐射防护剂相比，照前/后给药均能显著延长小鼠生存期。进一步机制研究显示CL429可能主要通过联合靶向TLR2/NOD2，还可能通过新途径发挥高效辐射损伤防治作用。本研究将在此基础上，拟通过体内外毒性实验进一步明确其安全性，并从分子、细胞、组织、活体多层次阐明CL429对辐射损伤的防治效应及其规律；采用基因敲除小鼠模型和高通量测序等技术手段分析CL429防治辐射损伤作用的信号转导途径，找出介导其防治辐射损伤作用的下游关键效应分子，并加以验证。对CL429防治辐射损伤机制的深入研究将有助于解决电离辐射损伤的关键难题；进一步明确CL429的临床应用价值，有望提供一种高效低毒的新型辐射损伤防治制剂，为我国重度电离辐射损伤救治难题寻找新的解决途径。

Severe ionizing radiation injury is world widely healthy threaten during the development of nuclear power application. Refer to our previous data and literature analysis, we screened a novel targeting ligand, CL429, which possessed good therapeutic effect on radiation injury and low toxicity. Our prior data showed that drug administration before/after radiation could both prolong mice survival and CL429 played its radiation protection role by combining target TLR2/NOD2 and unknown pathway. Our project will focus on the drug safety of CL429 and the role of CL429 on prevention and treatment of radiation injury. We will investigate the underlying mechanism of CL429 in molecules, cells, tissues and animal levels. We will identify the key molecules involved in underlying molecular mechanism by well-designed gene knock-out mice model. In conclusion, our project will investigate the role of CL429 in treatment of radiation injury and highlight the potential value in translational medicine. Meanwhile, the elucidation of the molecular mechanism of CL429 in radiation protection will provide a better understanding of the pathogenesis of radiation injury.