肝窦毛细血管化和肝内纤维间隔血管重构是影响肝纤维化进展及能否逆转的关键，我们前期对慢性乙肝患者基因芯片研究发现Notch信号通路随着纤维化进展明显增强，抑制Notch信号可降低窦内皮细胞毛细血管化。本研究建立四氯化碳肝纤维化及撤药后肝纤维化自发性逆转、胆管结扎诱导的急慢性肝损伤小鼠模型，通过计算机3D成像技术，观察急慢性肝纤维化形成过程及肝纤维化逆转过程中肝窦和纤维间隔新生血管形成及改建过程；分别通过肝脏选择性基因敲除小鼠和窦内皮细胞的Notch受体，观察不同信号活化和抑制后肝纤维化间隔血管重构及肝窦毛细胞血管化的变化；细胞实验分析Notch信号对活化肝星状细胞促进肝窦毛细血管化及增强内皮细胞血管形成能力影响；临床验证和分析慢性乙肝患者肝组织纤维间隔血管化和肝窦毛细血管化发生过程和发生机制，为肝纤维化发病机制和防治提供实验和临床依据。

Sinusoidal capillarization and fibrous septa vascularization are pivitol elements on the progress of liver fibrosis and its reversal. Our preliminary study demonstrated that Notch signalings are the main pathway enhancing with the increased extent of fibrosis by microarray analysis on chronic hepatitis B patients with different stages of liver fibrosis showed that inhibition of Notch signalings could decrease the the extent of sinusoidal capillarization of sinusoidal epithelial cells. In this study, we will establish the chronic or acute liver fibrosis model in mice induced by injection of carbon tetrachloride or bile duct ligation. we also will establish the mice model of spontaneous reversal of liver fibrosis by stopping the injection of carbon tetrachloride. We aim to investigate the dynamic changes of hepatic vasular system including sinusoidal capillarization and fibrous septa vascularization in the liver fibrogenesis and regression by computerized 3D remodelling techniques. We also want to explore the role of Notch signaling in the occurence and progression of sinusoidal capillarization and fibrous septa vascularization in mice by in vivo and in vitro experimens. Futhermore, we plan to confirm and explore the key mechnisms on hepatic vascular remodelling in the process of liver fibrosis on the basis of liver histological analysis in chronic hepatitis B patients. Therefore, we aim to provide clues for the formation, prevention and treatment of liver fibrosis.