NETs调控肝硬化门静脉高压症门静脉血栓的机制研究

Portal vein thrombosis is a very common complication of cirrhotic portal hypertension, especially in patients after splenectomy and devascularization. Moreover, PVT cause further liver damage. It is a potential therapy target to understand the pathology of portal vein thrombosis. It is widely considered that NETs promote thrombosis and induce liver damage. Our data revealed that more NETs in patients with portal vein thrombosis were detected than control. Based on those data, we want to study the mechanism of NETs in portal vein thrombosis by using PHT mouse model and clinical samples. Furthermore, whether NETs is a prognostic marker and therapy target for portal vein thrombosis will be investigated by interfering with NETosis. Last but not least, the effect of NETs components on portal vein thrombosis will be explored.

门静脉血栓是肝硬化门静脉高压症常见的并发症，尤其是经过脾切除加贲门周围血管离断术后的患者门静脉血栓发病率极高，门静脉血栓引起肝功能进一步受损加重门静脉高压症。能否分析血栓形成病因，并找到治疗门静脉血栓的新方法，是治疗门静脉高压症的关键点之一。国内外研究提示NETs能促进血栓形成，同时NETs能通过炎症反应介导肝损伤，我们的前期研究预实验显示存在门静脉血栓的患者外周血和肝内NETs含量高于对照组，提示NETs与门静脉血栓形成有关。本项目将在小鼠门高压模型与临床肝硬化门静脉高压症患者标本上，研究NETs在门静脉血栓发生机制中的作用，并通过干扰NETs形成，探索NETs作为预测血栓形成和治疗门静脉血栓靶点的可行性，并且深入寻找NETs相关组成成分与门静脉血栓形成的机制。

门静脉血栓是肝硬化门静脉高压症常见的并发症，尤其是经过脾切除加贲门周围血管离断术后的患者门静脉血栓发病率极高。我们的实验显示门静脉高压症合并门静脉血栓的患者外周血和肝内NETs含量高于门静脉高压患者，提示NETs与门静脉血栓形成有关。本项目在大鼠门高压模型与临床肝硬化门静脉高压症患者的外周血样本和肝脏标本中均发现大量NETs。首次建立门静脉高压合并门静脉血栓动物模型，在该模型中使用PAD4抑制剂干扰NETs形成，发现能改善门静脉血栓从而降低门静脉压力。