脓毒症严重威胁人类生命，亟需寻找治疗新靶点。肺脏是最易受累的器官之一，减轻脓毒症急性肺损伤对治疗脓毒症具有重要意义。我们前期研究发现，TR3/Nur77能减轻肺水肿程度，减少促炎性介质生成，在脓毒症中发挥关键性保护作用，但具体机制尚未明确。TR3/Nur77编码TR3异构体1（TR3-iso1）和TR3异构体2（TR3-iso2）两种蛋白，具有不同功能。LPS能显著增加TR3-iso1合成，提示TR3-iso1可能是TR3/Nur77通路的关键信号分子。为进一步明确TR3-iso1在脓毒症肺损伤中的作用，本课题从细胞模型、动物模型两方面，围绕炎症反应、上皮通透性和细胞凋亡等方面揭示TR3-iso1对脓毒症肺损伤保护作用的分子机制，并探讨p38/NF-kB相关通路信号转导途径及作用。该研究既能拓宽TR3/Nur77在脓毒症中作用的认识，也为脓毒症肺损伤的治疗提供新思路。

Sepsis is a serious threat to human health, thus it is important to find new treatment targets. The lung is one of the most vulnerable organs in sepsis. It is of great significance to prevent further progression of acute lung injury in the treatment of sepsis. Our previous studies had shown that TR3 (or murine Nur77) could decrease pulmonary edema, inhibit proinflammatory mediator formation, and played an important role in acute lung injury of sepsis. The specific mechanism, however, is still not clear. There were two TR3/Nur77 isoforms in human cells, with different biological functions, which were TR3 isoform 1 (TR3-iso 1) and TR3 isoform 2 (TR3-iso 2). Lipopolysaccharide could dramatically increase TR3-iso 1 synthesis, implying that TR3-iso1 might be a key molecular in TR3/Nur77 pathway. In order to clarify the role of TR3-iso1 in sepsis, we are planning to focus on inflammatory response, epithelial cell permeability, as well as apoptosis in cell and animal models and study the p38/NF-kB pathway to explore the molecular mechanism of TR3/Nur77-iso1 on septic lung injury，which may provide new evidence for the treatment of sepsis induced lung injury.