OGG1/PARP1在多环芳烃致肺损伤中的作用及机制研究

多环芳烃（PAHs）暴露是焦炉工人患呼吸系统疾病的主要原因，但PAHs致早期肺损伤的机制有待进一步探索。前期研究发现，焦炉工人DNA损伤和OGG1水平异常改变。我们推测，OGG1/PARP1的反馈调节，进而引起的Parthanatos死亡（PARP1依赖性死亡）发挥了重要作用。本项目以OGG1偶联的碱基切除修复通路和Parthanatos死亡通路为切入点，通过人群队列随访观察，明确OGG1/PARP1表达与PAHs暴露和早期肺损伤的关系；利用分子生物学和细胞生物学技术，建立Parthanatos死亡和OGG1异常表达的细胞模型，阐明OGG1/PARP1在PAHs致细胞Parthanatos死亡中的作用模式。人群与细胞相结合，揭示OGG1/PARP1在PAHs致肺损伤过程中的作用及其机制，为职业人群的健康监护及疾病预防提供理论依据。

Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) is the main cause of respiratory system disease of coke oven workers. However, the mechanism of PAHs induced lung injury still need to be explored. Based on the evidence of aberrant alterations of DNA damage and OGG1, we speculate the feedback regulation of OGG1/PARP1 and their function in Parthanatos (PARP1 dependent death) may play an important role. This study focus on the OGG1 coupled base excision repair pathway and Parthanatos pathway. Through population cohort follow-up observation, we will clarify the relationship between OGG1/PARP1, PAHs exposure and early lung injury. Then use the molecular biology and cell biology methods to establish cell models of Parthanatos and OGG1 abnormal expression. Using these cell models to verify the mechanism of OGG1/PARP1 in PAHs induced Parthanatos. Combined population study with cell experiment, this project will reveal the role and mechanism of OGG1/PARP1 in PAHs induced lung injury, so as to provide theoretical basis for the health surveillance and disease prevention of coke oven workers.