活血祛瘀的下瘀血汤是治疗肝纤维化有效经典方剂，BMP激活素膜结合抑制因子(BMP and activin membrane bound inhibitor，BAMBI)是炎症和纤维化的重要介体；本课题前期发现肝星状细胞（HSC）活化过程中有BAMBI核转位及BAMBI与Smad7结合减少而与Smad2/3结合增多，下瘀血汤对此有显著调控作用；提出“下瘀血汤可能通过调控BAMBI/Smads信号转导抗肝纤维化”的假说。为此，采用免疫荧光和核浆蛋白分离技术，通过CCl4肝纤维化模型观测BAMBI核转位/Smads信号转导的关联性及下瘀血汤干预前后的变化；结合hHSC培养，通过染色质免疫共沉淀测序、蛋白质免疫共沉淀等技术，分析BAMBI/Smads信号转导在HSC活化、肝纤维化病理机制中的作用以及下瘀血汤的干预效应，阐释下瘀血汤“活血祛瘀”抑制肝纤维化的病理生物学机制，为其发展应用奠定基础。

With the promoting blood circulation for removing blood stasis of Xia-yu-xue decoction (XYXD), is an effective classical prescriptions in liver fibrosis treatment. BMP and activin membrane bound inhibitor (BAMBI) plays an important role in inflammation and fibrogenesis. We previously proved that BAMBI translocated from cytoplasm to nucleus, and the combination of BAMBI and Smad7 reduced significantly but the binding of Smad2/3 and BAMBI increased notably in HSC activation in response to LPS stimulation, and XYXD could regulate remarkably these pathological changes. Based on these new findings, we hypothesized that XYXD inhibit liver fibrosis by regulating on BAMBI/Smads signal transduction. For these aims, we would detect the inhibitory effects of XYXD on BAMBI nuclear translocation and Smads signal transduction and their relationships using immunofluorescence microscopy and nuclear/membrane separation in CCl4-indcued liver fibrosis in mice. Next, we would analyze the function of BAMBI/Smads signal transduction in HSC activation and fibrogenesis, meanwhile; we would explore the regulation of XYXD on these changes using primary human stellate cells and fibrotic model by chromatin immunoprecipitation (ChIP) sequence and co-immunoprecipitation. The project will help us to elucidate the pathological biological mechanism of XYXD on inhibiting liver fibrosis by promoting blood circulation for removing blood stasis principle, and laying a foundation for its further development and clinical application.