放射性食管损伤是肿瘤放疗的常见并发症，严重影响患者生存质量。但食管放射敏感性的影响因素尚不完全清楚。本项目前期研究发现前列腺素D2（PGD2）含量在受照射大鼠食管组织中显著增加，伴随着其合成关键酶COX-2表达及S-亚硝基化修饰水平的升高，COX-2抑制剂Celecoxib对受照射食管上皮细胞具有潜在保护作用。项目组根据前期研究及文献报道提出科学假说：电离辐射促进COX-2的S-亚硝基化修饰，增强其催化活性，调控PGD2合成，激活下游受体CRTH2，影响放射性食管损伤进展。本项目拟从分子、细胞和动物水平上进一步阐明：1）COX-2/PGD2/CRTH2途径对食管上皮细胞放射敏感性及动物模型放射性食管损伤的影响；2）受照射食管上皮细胞中S-亚硝基化修饰对COX-2活性及PGD2合成的调控作用及分子机制。本项目有望揭示电离辐射诱发食管损伤新的分子机制，为防治放射性食管损伤提供新的靶点和策略。

Radiation-induced esophageal injury is a common complication of radiotherapy, which seriously affects the life quality of patients. However, the mechanisms underlying esophageal radiosensitivity remain limited. In our preliminary study, we found that prostaglandin D2 (PGD2)、the expression and S-nitrosylation of key enzyme COX-2 were significantly increased in the esophagus of irradiated rats, and COX-2 inhibitor Celecoxib had a potential protective effect on the irradiated esophageal epithelial cells. According to previous studies and literature reports, we proposed a scientific hypothesis: radiation promotes S-nitrosylation of COX-2, enhances its catalytic activity, regulates the synthesis of PGD2, activates the downstream receptor CRTH2, and affects the progression of radiation-induced esophageal injury. This project aims to further clarify the following issues at the molecular, cellular and animal levels: 1) The effect of COX-2/PGD2/CRTH2 metabolic pathway on the radiosensitivity of esophageal epithelial cells and the progression of rat radiation-induced esophageal injury; 2) The mechanism of S-nitrosylation in regulating COX-2 activity and PGD2 synthesis in irradiated esophageal epithelial cells. This project is expected to reveal a new mechanism of radiation-induced esophageal injury, which may provide new targets and strategies for the prevention and treatment of radiation-induced esophageal injury.