肺血管炎症反应是低氧性肺血管结构重构形成的重要环节，但低氧刺激肺血管炎症发生的分子机制尚不清楚。本课题组前期研究发现二氧化硫(SO2)抑制低氧性肺血管结构重构。因此，本课题将进一步探索低氧性肺血管结构重构中内源性SO2/AAT体系与肺血管炎症反应的动态变化；在血管内皮特异性AAT转基因及敲除小鼠中，研究激活或抑制内源性SO2生成对低氧性肺血管炎症反应的影响；通过抑制原代肺动脉内皮细胞NF-κB通路及小鼠血管内皮细胞特异性p65基因敲除，揭示NF-κB通路在SO2抑制低氧性肺血管炎症反应中的作用；通过特异性巯基及巯基氧化修饰探针、质谱分析和点突变技术，阐明SO2对p65蛋白cys38巯基的氧化修饰作用。通过上述研究，以期揭示SO2 对低氧性肺血管结构重构形成中肺血管炎症反应的调节作用、信号通路及分子机制，深化低氧性肺血管结构重构的炎症调节理论，并为寻找肺动脉高压治疗的炎症干预靶点提供新思路。

Pulmonary vascular inflammation is an important process in the development of hypoxic pulmonary vascular structural remodeling. However, the mechanisms responsible for pulmonary vascular inflammation induced by hypoxia have been unclear. The applicant’s previous studies demonstrated that endogenous sulfur dioxide (SO2) inhibited pulmonary vascular structural remodeling. The present study is, therefore, designed to investigate the dynamic changes in endogenous SO2/aspartate aminotransferanse (AAT) pathway and pulmonary vascular inflammatory response in rats with hypoxic pulmonary vascular structural remodeling. By activating and inhibiting the endogenous SO2 pathway in the vascular endothelium specific AAT transgenic or knockout mice, the study is designed to elucidate the effect of activation or inhibition of endogenous SO2 production on hypoxic pulmonary vascular inflammatory response. Furthermore, the role of NF-κB pathway in the inhibition of hypoxic pulmonary vascular inflammatory response by sulfur dioxide is to be determined by inhibiting NF-κB pathway in hypoxic primary human pulmonary artery endothelial cell or in vascular endothelium specific AAT knockout mice. By using sulfhydryl specific and sulfhydryl oxidation specific probes, mass spectrometry analysis and site-directed mutation technology, sulfhydryl oxidation of NF-κB p65 and its localization is to be examined. The above studies would deepen the understanding of the role of SO2 in pulmonary vascular inflammatory response, its signaling pathway, molecular mechanisms and the regulatory theory of hypoxic pulmonary structural remodeling and provide new research strategy for discovering therapeutic target of pulmonary hypertension.