急性肺损伤（ALI）是指各种致伤因素导致弥漫性肺间质及非心源性肺水肿并形成严重的低氧血症，其核心病理改变为肺微血管内皮细胞和肺胞上皮细胞所形成的肺气血屏障的损害。已知组织因子-凝血酶信号通路在肺微血管内皮细胞损伤中起到关键作用，但在ALI过程中如何实现靶向抗凝及其作用机制并不清楚。同时我们发现mTOR-细胞自噬信号通路可能在ALI过程中起到关键调控作用，但在不同的细胞中其功能和效果可能不同。因此，本课题以mTOR-细胞自噬以及组织因子-凝血酶信号通路及其相互作用为主要靶点，利用mTORf/f、Beclin+/-、LC3B-/-、以及靶向抗凝的CD31-Hir(TFPI)-Tg等小鼠，通过骨髓移植、ALI整体动物模型、体外细胞培养等方法，研究这两条关键信号通路对病原体感染诱导的ALI发生发展过程中气血屏障损伤以及粒单核细胞分化和功能的调控作用，为开发研究治疗ALI新的药物靶点。

Acute lung injury (ALI) is characterized by diffuse interstitial infiltrates, oedema, and severe hypoxemia, primarily due to the damaged air-blood barrier between pulmonary microvascular endothelium and alveolar epithelium and subsequently increased vascular permeability. The tissue factor-thrombin pathway has been suggested to play a pivotal role in regulation of microvascular endothelial injury, however, due to that inhibition of this pathway may lead to systemic bleeding, it is therefore of great importance to find out cell specific anticoagulants for ALI and to investigate the underlying mechanisms. We have also found that mammalian target of rapamycin (mTOR)-autophagy pathway plays important roles in ALI, while it may have different functions and exert different effects in different cell types. In the current project, we plan to investigate the critical roles of these two pathways and their interactions in regulation the damage of microvascular endothelial cells and alveolar epithelial cells and the differentiation of function of granulocytes during ALI pathogenesis, by utilizing the mTORf/f, Beclin+/-, LC3B-/-, and cell specific anticoagulant CD31-Hir(TFPI)-Tg mice, and through experimental techniques such as bone marrow transfer, ALI animal.models, and cell cultures, which would provide theoretical base for new therapeutic targets of ALI.