肺血管内皮细胞连接损伤导致的毛细血管漏是ARDS的主要原因，尚无有效治疗措施。研究发现内皮细胞PECAM-1存在独特的“扩散性诱陷”效应，生理情况下均被“诱陷”分布于细胞连接处，而在炎症刺激下，PECAM-1可再分布至管腔面。申请者前期研究发现，急性肺损伤时血小板PECAM-1黏附于肺血管内皮细胞管腔面PECAM-1，导致内皮细胞连接断裂。据此提出：血小板触发血管内皮细胞管腔面PECAM-1“扩散性诱陷”效应，介导肺毛细血管漏的假说。本研究拟通过输注PECAM-1+血小板，观察活体肺组织，研究血小板是否参与肺毛细血管漏形成；通过沉默、过表达肺血管内皮细胞PECAM-1，研究PECAM-1+血小板通过管腔PECAM-1“扩散性诱陷”发挥作用；最后阻断管腔PECAM-1信号传导通路研究其诱发肺毛细血管漏的机制，为调控毛细血管漏及治疗ARDS提供新的理论依据。

Capillary leakage was the main reason of acute respiratory distress syndrome（ARDS）, which is short of the effective therapeutic strategies until now. Studies have demonstrated PECAM-1 was ‘captured’ at cellular con-junction to keep endothelial barrier by “diffusion trapping” of endothelial PECAM-1. However, PECAM-1 would redistribute to luminal surface under insult of inflammation, and platelet adhered to lung endothelium via PECAM-1-PECAM-1 interaction. As a result, endothelial junctions were broken to induce ARDS, as we found in our pilot study. Thus we hypothesized that platelet mediated pulmonary capillary leakage via triggering “diffusion trapping” in the pulmonary endothelial luminal PECAM-1. To test the hypothesis, PECAM-1+ platelets would be injected into mice to investigate the effect of PECAM-1+ platelet on pulmonary capillary leakage. Then PECAM-1 on pulmonary vascular endothelial cells would be silenced or over-expressed to determine whether PECAM-1 on endothelial cells is involved in capillary leakage via triggering “diffusion trapping”. At last, PECAM-1 signal pathways in both platelet and endothelial cells would be blocked to elucidate the mechanisms of PECAM-1 in pulmonary capillary leakage. Our research would be helpful to explore the effective intervention targets and strategies for ARDS.