重叠综合症模式低氧通过S1P/HDAC信号调控肺部炎症的机制研究

呼吸重叠综合征(Respiratory overlap syndrome, OS)即阻塞性睡眠呼吸暂停综合征合并慢性阻塞性肺病，发病率高且危害大，而目前关于OS的炎症发病机制尚不完全清楚。既往研究表明OS同时存在间歇低氧和持续低氧状况，与此同时，炎症是OS各种并发疾病的病理基础。 .我们在前期研究中发现，S1P/HDAC信号通路可以诱导巨噬细胞向M1方向分化，而后者在慢性阻塞性肺病中发挥了重要作用。本课题拟在此基础上进一步探讨间歇性低氧对S1P/HDAC信号通路及肺泡巨噬细胞分化的调控，以及对OS疾病进程的影响，并探索能有效干扰OS疾病进展的措施。我们将从临床OS患者、间歇伴持续低氧暴露动物和体外分离的巨噬细胞三个层次展开研究，重点探讨S1P/HDAC对肺泡巨噬细胞的分化调控和在OS性肺炎中的作用机制。本项目的顺利实施将会为OS患者的发病机理揭开新的视角，也将为OS的临床治疗提供新的参考。

The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), termed the overlap syndrome (OS）. Incidence rate of OS is high and its harm is great. At present, the pathogenesis of OS is not fully understood. Previous studies have shown that intermittent hypoxia and persistent hypoxia exist simultaneously in OS. At the same time, inflammation is the pathological basis of various complications of OS..In our previous studies, we found that S1P / HDAC signaling pathway can induce macrophages to differentiate into M1, which plays an important role in COPD. On this basis, we will further explore the regulation of intermittent hypoxia on S1P/HDAC signaling pathway and alveolar macrophage differentiation, as well as the impact on the progression of OS disease, and explore measures that can effectively interfere with the progression of OS disease. We will focus on the regulation of S1P / HDAC on the differentiation of alveolar macrophages and its mechanism in OS pneumonia. The successful implementation of this project will open a new perspective for the pathogenesis of OS patients, and also provide a new reference for the clinical treatment of OS.