乙型肝炎病毒引起宿主异常的免疫应答和凝血功能紊乱是慢性重型乙型肝炎（慢重肝）重症化的关键环节。我们前期工作已初步证实：慢重肝红细胞发生过度衰亡导致红细胞微粒（RMPs）释放升高，肝组织明显形成微血栓。既往观点认为RMPs是一些无意义的细胞碎片，近年研究发现RMPs在促炎症反应和促微血栓形成中发挥了重要作用。为揭示RMPs在慢重肝肝损伤中的作用及机制，本项目将分别在体内外水平证实慢重肝患者红细胞出现衰亡、RMPs具有促炎和促凝血作用的基础上，采用定量蛋白质组学技术筛选并鉴定RMPs组分中关键促炎相关蛋白（IPs），通过建立转染IPs基因的人单核巨噬细胞株和小鼠肝衰模型，从临床样品、细胞和动物水平分析RMPs诱导炎症反应和促进凝血而加重肝损伤的分子机制。项目预期结果有助于深入阐明慢重肝免疫发病机制，并为防治慢重肝提供新的思路和方法。

The outcome of hepatitis B virus (HBV)-induced liver injury is largely determined by immune-mediated host-virus interactions and coagulation disorders. The disturbed immune response and blood clotting play a pivotal role in the pathological processes of chronic severe hepatitis B. Our previous studies showed that excessive red blood cells (RBC) eryptosis could be observed in patients with chronic severe hepatitis B, with an elevated number of red blood cell-derived microparticles（RMPs). And the microthrombosis is usually obvious in hepatic tissue of patients with chronic severe hepatitis B. Initially, the RMPs have been considered as a type of cell debris without any biological functions. However, these RMPs are now recognized as being involved in a broad spectrum of pathological activities including promoting inflammation and microthrombosis. Here, we aim to elucidate the role and mechanisms of RMPs in chronic severe hepatitis B-mediated liver injury. Studies will be carried out in vivo and in vitro to show:1) the increased number of RBC eryptosis in patients with chronic severe hepatitis B. 2) the pro-inflammation and pro-coagulant effects of these RMPs. Moreover, quantitative proteomics techniques will be used to screen and identify the key pro-inflammation-associated proteins (IPs) in RMPs. Using the human macrophage cell line U937 or THP-1 with an enforced expression of IPs and mice model of liver failure, the molecular mechanisms of RMPs-mediated liver injury via promoting inflammation and microthrombosis will be investigated in vivo and in vitro. These efforts will allow us to elucidate the detailed mechanisms involved in HBV-mediated liver injury, thus provide new sights into the prevention and treatment of chronic severe hepatitis B.