血管渗漏是导致临床脓毒症患者出现多器官功能障碍综合症，甚至死亡的主要原因。Mfn2（mitofusin2）作为线粒体融合蛋白，其表达和活性的异常除了可通过介导线粒体融合障碍参与多种疾病的调控外，还可作为胞浆信号分子参与细胞增殖等多种功能的调节。Mfn2是否参与脓毒症血管渗漏的调节，未见报道。通过文献分析和前期预实验，推测Mfn2可能在脓毒症血管渗漏的发生中有重要作用。其机制可能与Mfn2以非线粒体依赖方式，通过Dynamin-1调控Caveolin-1以穿细胞途径，和通过SP1调控Cx43以旁细胞途径参与脓毒症血管渗漏的调控。为此，本项目拟采用CLP复制脓毒症模型，通过整体动物、离体细胞，采用蛋白组学、分子生物学及电镜等技术，研究Mfn2在脓毒症血管渗漏发生中的作用及其机制。本研究将从线粒体相关蛋白角度解释脓毒症血管渗漏的发生机制，为脓毒症血管渗漏的防治提供了新的靶点。

Vascular hyperpermeability mainly causes multiple organ dysfunction syndrome, even leading to death in sepsis. Mitofusin2 (Mfn2), known as a protein mediating mitochondria fusion, takes part in occurrence of many kinds of diseases. Moreover, Mfn2 also is a intercellular signaling molecules regulating cell proliferation. however, The effect of Mfn2 on regulation of vascular hyperpermeability after sepsis is unclear. Based on documentary analysis and pre-experiment results, we propose the hypothesis that Mfn2 plays important role in regulation of vascular hyperpermeability thought trans-endothelial pathway via Dynamin-1/caveolin-1 and para-cellular pathway via SP1/Cx43 after sepsis. To test this hypothesis, we will use cecal ligation and puncture (CLP) induced septic rats and lung vein endothelial cells (VECs) to investigate the role of Mfn2 in regulation vascular hyperpermeability after sepsis and the its mechanism. The main objective tends to raise the new mechanism to explain the occurrence of vascular hyperpermeability after sepsis, and provide the new therapeutic targets and modulation strategy for.clinical critical conditions such as severe trauma and shock.