TRAF7在急性肺损伤中的功能和机制研究

急性肺损伤（ALI）是一种呼吸重症疾病，死亡率高，治疗效果差。ALI发病机制复杂，其中内皮细胞功能紊乱至关重要。TRAF7在肿瘤、脊髓损伤等疾病中具有重要的功能，但是在急性肺损伤中的作用并无报道。本项目前期研究发现，在LPS诱导的小鼠急性肺损伤模型中，TRAF7的表达显著下调，TRAF7全身性基因敲除显著促进急性肺损伤发展。但是TRAF7是否通过调节内皮细胞功能调控急性肺损伤的发展以及其分子机制尚不清楚。本项目拟通过构建内皮细胞特异性TRAF7基因敲除和转基因小鼠，阐明内皮特异性TRAF7对急性肺损伤的调控作用，并分离原代肺血管内皮细胞，研究TRAF7对内皮细胞的炎症反应、凋亡以及通透性的影响，最后应用转录组学和蛋白组学联合分析寻找TRAF7调节内皮细胞功能以及急性肺损伤功能的分子机制，以期为寻找防治急性肺损伤的药物靶点提供重要的理论基础。

Acute lung injury (ALI) is a severe respiratory disease with high mortality and poor therapeutic effect. The pathogenesis of ALI is complex, and the dysfunction of endothelial cells is key event. TRAF7 plays an important role in tumors, spinal cord injury and other diseases, but its role in acute lung injury has not been reported. In this current study, we found that the expression of TRAF7 was significantly down-regulated in LPS-induced acute lung injury model in mice, and that global gene knockout of TRAF7 significantly promoted the development of acute lung injury. However, whether TRAF7 regulates the development of acute lung injury by regulating endothelial cell function and its molecular mechanism remains unclear. This project aims to elucidate the regulatory effect of TRAF7 on endothelial cell and acute lung injury by constructing endothelial cell-specific TRAF7 gene knockout and transgenic mice, and to study the effects of TRAF7 on inflammatory response, apoptosis and permeability in endothelial cells by isolating primary pulmonary vascular endothelial cells. Finally, the molecular mechanism of TRAF7 on regulating endothelial cell function and acute lung injury function was explored by combining transcriptional histology and proteomics analysis, in order to provide an important theoretical basis for finding drug targets to prevent and treat acute lung injury.