脓毒症相关凝血障碍（SIC）是脓毒症常见的并发症，单纯抗凝治疗无法从根本上改变不良预后，明确调控SIC的具体机制和关键分子至关重要。内皮细胞是血栓-炎症重要的作用界面，我们前期研究发现：血小板内皮细胞粘附分子-1（PECAM-1）是介导内皮细胞屏障和炎症功能的重要靶点，PECAM-1 Leu125Val基因多态性（SNP）与SIC患者的死亡率相关。在内毒素刺激下，PECAM-1 Leu125Val 亚型可影响内皮细胞通透性屏障的修复和炎症反应。因此本项目假设，PECAM-1 Leu125Val SNP通过调控血管内皮屏障功能和炎症反应介导脓毒症凝血功能紊乱。本项目中，我们拟在细胞层面和脓毒症小鼠模型中进一步证实PECAM-1 Leu125Val SNP对内皮细胞的调控作用，明确对凝血功能和炎症反应的影响和机制，为治疗脓毒症相关凝血障碍和改善脓毒症预后提供新的思路。

Sepsis-induced coagulopathy (SIC) is one of the common complications in sepsis, and anticoagulant therapy is unable to reverse poor prognosis. It is important to investigate the mechanisms of SIC. Endothelial cells form the essential interactive surface for thrombosis and inflammation. Our previous studies have found that platelet endothelial cell adhesion molecule 1 (PECAM-1) was the vital target for endothelial barrier and inflammation functions, and PECAM-1 single nucleotide polymorphisms (SNP) was associated with mortality in SIC patients. Based on our preliminary data, we propose that PECAM-1 Leu125Val SNP affects sepsis-induced coagulopathy by mediating endothelial barrier and inflammation. In this project, we plan to define the endothelial modulation of PECAM-1Leu125Val SNP, and explore the role and mechanism of PECAM-1 SNP in endothelial cell-mediated coagulation and inflammation using in vitro and in vivo models. Successful completion of experiments outlined in this proposal will provide novel therapeutic strategies and targets for SIC and improve prognosis of sepsis.