促进炎症消退是炎症治疗的理想策略，巨噬细胞吞噬凋亡的炎症细胞是炎症消退的重要方式。巨噬细胞具有多功能性和异质性，巨噬细胞极性从M1向M2漂移可以促进炎症消退和组织修复。我们前期研究发现血管生成素1（Ang1）促进内毒素性肺损伤炎症消退，但其对巨噬细胞极性的影响及机制尚不清楚。本项目拟在我们前期研究的基础上，通过观察在小鼠气管滴入脂多糖后不同时间点Ang1对肺泡巨噬细胞表面F4/80抗原表达和肺泡灌洗液中不同极性的巨噬细胞相关因子表达的影响，证实Ang1具有促进肺泡巨噬细胞极性从M1向M2漂移的作用。再在体外实验中观察Ang1对PI3K信号通路的调节作用，通过LY294002特异性阻断PI3K信号通路揭示该信号通路在Ang1促进肺泡巨噬细胞极性漂移中的作用，深入的阐明Ang1促进内毒素性肺损伤炎症消退的机制，丰富炎症消退理论，同时为进一步研究Ang1在机体免疫调节和代谢调节中的作用奠定基础。

Promoting inflammation resolution is an ideal strategy for the inflammation therapy. The phagocytosis of apoptotic inflammatory cells by phagocytes is the main mechanism of inflammation resolution. Phagocytes are dynamic and heterogeneous cells with different polarizations, including M1 phenotype, M2 phenotype and regulatory phagocytes. M1 macrophages are microbicidal and inflammatory (postinfectious pathogenesis), M2 macrophages are immunomodulators and take part in the inflammation resolution, tissue restoration and repair with anti-inflammatory effect. The polarization shift of macrophages will be of great benefit to accommodate the different stages of inflammation. We have found in earlier research that angiopoietin-1 could accelerate the inflammation resolution in endotoxic acute lung injury in mice by promoting the nuetrophil apoptosis and its phagocytosis by macrophage cells. But the effect of angiopoietin-1 on the polarization shift of macrophage cells and the underlying mechanism are unclear. This item will first explore the effect of angiopoietin-1 on the expression of different macrophage phenotypes associated factors, type-1 and type-2 helper T-cell cytokines in the bronchoalveolar lavage fluid with ELISA kits or polymerase chain reaction method, including IL-1β, TNF-α, L-arginine, IL-10, TGF-β, IFN-γ, IL-4, IL-13. At the same time, we will analyze the F4/80 antigen expression on the macrophage cells with Flow Cytometry method in vivo. Then we observe the modulating effect of angiopoietin-1 on the PI3K signal pathway and whether this pathway takes part in the polarization shift of macrophage cells through specific blocking the PI3K signal pathway with LY294002 in vitro. In this way, we could deeply discover the mechanism of angiopoietin-1 promoting the inflammation resolution in endotoxic acute lung injury in mice and further enrich the theory of inflammation resolution. At the same time, it would pave a solid foundation for further exploration of the effect of angiopoietin-1 on the immune and metabolic modulation in acute lung injury.