Ang1/Tie2轴在脓毒症DIC中调控血栓形成和维持血管内皮细胞稳态的分子机制研究

脓毒症弥散性血管内凝血（DIC）严重危害人类健康，但缺乏早期标记物和有效的治疗手段。目前研究表明Ang1/Tie2轴失调与脓毒症DIC和血管内皮细胞稳态密切相关，并根据项目前期研究基础提示Ang1/Tie2轴参与调控血管内皮细胞稳态并在脓毒症的早期起着重要的调节血栓形成的作用，但其分子机制还有待深入研究。为此，本项目提出Ang1/Tie2轴通过调控凝血酶原酶激活凝血酶以对抗血栓的形成并协同PECAM-1维持内皮细胞稳态这一科学假说。本项目拟通过研究Ang1/Tie2轴在炎症损伤模型中影响凝血酶生成的分子机制，探寻识别早期DIC的标志物，鉴定Ang1和Tie2的抗血栓作用，探究Ang1与PECAM-1维持细胞稳态的分子机理，为深入理解Ang1/Tie2轴在脓毒症DIC中调控血栓形成和维持血管内皮细胞稳态的机制奠定基础，同时为脓毒症DIC的早期诊治提供新的思路和靶点。

Septic disseminated intravascular coagulation (DIC) seriously endangers human health, but lacks early biomarkers and effective treatments. Studies have shown that the dysregulation of Ang1/Tie2 axis is closely related to septic DIC and vascular endothelial cell homeostasis, and according to the preliminary results of this project suggest that the Ang1/Tie2 axis plays an important role in the regulation of thrombosis caused by septic DIC and the maintenance of endothelial cell homeostasis, but its molecular mechanism remains unclear. This project proposes a hypothesis: the Ang1/Tie2 axis fights thrombus formation by regulating prothrombinase to activate thrombin, and maintain endothelial homeostasis by coordination with PECAM-1. This project aim to study the molecular mechanism of Ang1/Tie2 axis affecting thrombin formation in inflammation models, to identify pre-DIC markers and antithrombotic effects of Ang1 and Tie2, and to elucidate the mechanism of Ang1 maintaining vascular endothelial cells with PECAM-1. The knowledge gained from this project will not only provide in-depth information to lay a foundation for further understanding of the mechanism of Ang1/Tie2 axis in regulating thrombosis and maintaining vascular endothelial cell homeostasis in septic DIC, but also provide new ideas and targets for the early diagnosis and treatment of septic DIC.