疏肝健脾活血方调控VEGF-Notch信号通路抑制肝纤维化过程中血管新生的作用机制研究

肝纤维化是继发于各种形式慢性肝损伤之后的组织修复反应，若无有效治疗将演变为肝硬化和肝癌。肝纤维化进程中存在明显的病理性血管新生与重构，阻碍了肝纤维化的逆转与恢复。血管新生及其信号调控系统已成为肝纤维化治疗的潜在靶标。研究发现VEGF与Notch信号通路能相互调节共同影响血管新生，但其在肝纤维化血管新生中的机制尚不明确。本课题以VEGF-Notch信号通路在肝纤维化进程血管新生中的相互关系和作用为切入点，体内动态观察大鼠肝纤维化形成过程中VEGF、Notch信号通路的相互作用及疏肝健脾活血方的干预作用；体外分别激活和阻制Notch通路、pcDNA3.1-VEGFl65质粒瞬时转染激活VEGF通路，应用免疫组化、免疫荧光、透射电镜、western blot 和RT-PCR等多种实验技术，观察分析疏肝健脾活血方抗肝纤维化血管新生的具体影响环节或靶点，为中医药防治肝纤维化提供新的研究思路和方法。

Liver fibrosis is secondary to various forms of chronic liver injury after the tissue repair response, will develop into liver cirrhosis and liver cancer without effective treatment. In the process of liver fibrosis is a clear pathological angiogenesis and reconstruction, hindered the reversal and recovery of liver fibrosis. Angiogenesis and its signal transduction system have become potential targets of liver fibrosis treatment. Studies have found that VEGF and Notch signaling pathways can accommodate each other mutual influence angiogenesis, but its mechanism is unclear in the angiogenesis of hepatic fibrosis. This topic with VEGF - Notch signaling pathway in the liver fibrosis process the mutual relations and the role of angiogenesis as the breakthrough point, dynamic observation in vivo rat liver fibrosis formation in the process of VEGF, and the interaction between Notch signaling pathway and Suganjianpihuoxue repice The intervention of the role; In vitro activation and resistance of Notch,transient transfection pcDNA3.1 - VEGFl65 plasmid activation of VEGF, using variety of experimental technology as immunohistochemical, immunofluorescence, transmission electron microscopy (sem) and westernt blot and rt-pcr and so on to analyze the Suganjianpihuoxue repice resisting the specific influence angiogenesis link or targets of hepatic fibrosis, new research ideas and methods will be found to preventiig and treating liver fibrosis with traditional Chinese medicine.