放射性肺损伤的早期预警和有效防治对于肿瘤放疗的顺利进行及应对核事故等具有重要意义。四氢生物蝶呤（BH4）为三磷酸鸟苷的代谢产物，是体内多种酶的重要辅酶或辅因子，但其在放射性肺损伤中的作用尚不清楚。本项目前期研究发现电离辐射能将BH4氧化成为二氢生物蝶呤（BH2）及其它代谢产物，这些代谢产物的种类及含量一方面反映了肺组织受照射剂量，另一方面能进一步影响细胞内自由基水平并加重辐射引起的氧化损伤。本项目拟在前期研究基础上采用多种手段揭示：1）不同剂量照射后不同时间BH4代谢产物种类及含量的变化规律；2）辐射产生的BH4代谢产物对放射性肺损伤进展的影响；3）设计开发新型基于表面增强拉曼散射技术（SERS）的平台来精确定量组织和血清中BH4及其代谢产物，实现放射性肺损伤的早期预警。本项目有望从BH4代谢产物的角度揭示放射性肺损伤新的进展机制，并提供一种基于SERS技术的放射性肺损伤早期预警监测手段。

Prevention, treatment and early-warning of radiation-induced lung injury are important for the radiotherapy of cancer patients and counteracting nuclear accidents. Tetrahydrobiopterin (BH4) is an important co-factor of nitric oxide synthase, which is closely related to the production of free radicals in cells. Our preliminary data showed that ionizing radiation aggravated the oxidation of BH4 to BH2 and other metabolites. These BH4 metabolites on the one hand represented the doses of radiation to lung, on the other hand might induce a secondary wave of free radicals and aggravate oxidative damage in lung cells. This project is based on the previous study to illustrate the following issues: 1) Exploring the influence of the type and content of BH4 metabolites in different doses of radiation; 2) The effects of metabolites of BH4 following radiation on the progression of radiation-induced lung injury; 3) Design and development of a novel technique based on surface-enhanced Raman scattering (SERS) to accurately detect tissue and serum BH4 and its metabolites content and proportion, to realize the early-warning of radiation-induced lung injury. This project is expected to reveal the new progress mechanism of radiation-induced lung injury from the perspective of BH4 metabolic pathway, and provide an early-warning and monitoring method based on SERS technology.