2008年国外学者发现激活TLR5对受照射小鼠具有很好的防护作用，为利用TLRS防治辐射损伤开辟了一条全新的研究思路。TLR9也是TLRs家族的重要成员，其介导的信号转导途径与TLR5类似，通过募集MyD88、IRAKs等分子，激活NF-κB和磷酸化IRAK1，诱导I型干扰素等的表达。我们的前期研究发现TLR9激动剂CPG-ODN对γ射线损伤造血系统和肠道系统具有明确治疗作用，提示TLR9是潜在重要的辐射治疗新靶点。本项目拟利用CPG-ODN激活TLR9信号分子,进一步研究其对不同射线和不同组织的辐射治疗效果，并对其治疗效果进行比较：1. 胸部肿瘤放疗时容易发生放射性肺炎，观察CPG-ODN对放射性肺损伤的治疗效果；2、高LET射线目前尚无有效治疗药物，研究其对高能粒子（高LET射线）辐射损伤治疗效果并同低LET射线(γ射线)进行比较。评价TLR9信号分子作为不同电离射线导致的辐射损伤防治新靶点的研究前景，为其激动剂CPG-ODN作为新型辐射防治药物提供理论基础和实验依据。

In 2008, Burdelya reported that activating Toll-Like Receptor 5(TLR 5) agonist CBLB502, a polypeptide derived from Salmonella flagellin,effectively protected mice from radiation damage.It mitigated radiation-induced damages both on gastrointestinal and hematopoietic systems,and the survival rate was also increased when CBLB502 was administrated pre- or post-irradiation. The radioprotective effects was thought to be due to the activation of increased nuclear factorκB(NF-κB) levels. As one of the most critical members is TLRs family,TLR9 shares extensive homology with TLR5, which promoted us to verify the potential radioprotective effect of TLR9 angonist Cytosine phosphate Guanosine oligodeoxynucleotides (CpG-ODN). Containing unmethylated cytosine-guanine motifs, CpG-ODN could also activate NF-κB through activating MyD88、IRAKs signaling pathway, thus induced the expression of IFN-I. Previously, we have demonstrated that CpG-ODN effectively mitigated toxicity induced by 60Co-γ-irradiation in mice through TLR9 actication, indicating that TLR9 might be a novel target for radiation sickness.In this project,through CPG-ODN activation of TLR9, we will investigate the therapy effct by the CPG to different radial and different tissue. And wo also will compare the therapy effect in the injure induced by different radial. Firstly, Radiation-induced lung injury (radiation pneumonitis and radiation pulmonary fibrosis) occurred often ,when radiotherapy was used in thoracic tumor. We will study the therapy effect of CPG-ODN to the radiation pneumonitis and radiation pulmonary fibrosis. Secondly, there are not effective therapy drug in the high LET radial at present. We will investigate the therapy effect of CPG-ODN to the injury induced by high LET radial and compare the difference between the low LET and high LET radial. This will provide us a novel target for radioprtection and also provide us strong experimental evidence for CPG-ODN as a novel radioprotectant.