本课题针对肝纤维化研究的新进展与中药复方抗肝纤维化的优势及存在的问题，提出“发现中药复方复杂成分主要效应化合物的组方是研究其有效调节纤维化复杂病理改变的前提，针对其核心病理变化可解析主要有效成分复方配伍原理”的假说。拟以疗效确切并已通过美国Ⅱ期临床试验、前期基础研究较扎实的FZHY方为对象，以其药效物质基础及对肝窦内皮细胞(LESCs))损伤与肝星状细胞(HSCs)活化之间双向信号传递机制影响为切入点，通过①基于体内过程的药效物质研究；②经LSECs去分化、HSCs活化及其相互作用的活性成分高内涵筛选；③均匀设计和验证实验获得最佳有效成分新复方并解析配伍效应；④新成分复方调控LSECs-HSCs相互作用的抗肝纤维化协同配伍效应机制的解析等四步分层次研究，以期明确该方抗肝纤维化对LESCs损伤与HSCs活化之间相互作用病理机制影响的主要物质基础及其效应的关键通路。为推进其国际化提供坚实基础。

Based on the explicit anti-fibrosis curative effect of traditional Chinese herbal formula Fuzheng-huayufang (FZHY) on cirrhosis patients and its in-depth basic researches previously, which has passed phaseⅡ clinical trials in United States, we proposed the hypothesis "focus on the main active components discovery in traditional Chinese medicine formula effectively regulating the complex pathology of liver fibrosis can resolve the main active ingredients compatibility principle and it’s mechanism of action (MOA) of anti-fibrosis". Cconsidering the complex pathological mechanism in liver fibrosis and the key role of bidirectional transmission between liver sinusoidal endothelial cell (LESCs) injury and hepatic stellate cells (HSCs) activation in pathopoiesis and progression of liver fibrosis, we propose a meaningful research project as follows: To analyze the changes of the contents of main components from FZHY in the samples of different tissues after oral administration to analysis the active components; Separating both primary LESCs and HSCs, and co-culturing those cells in vitro to screen the main effective components with High Content Screening; basing on the systematic analysis in filter results to develop the combination among active ingredients, verify the anti-fibrosis efficacy on liver fibrosis model using uniform design to find the effective formula; then adopting and analyzing on CCl4 and bile duct ligation models with specific gene knockout in LESCs which regulates the regeneration and fibrosis in liver; co-culturing the LESCs and HSCs with active components to explore the synergistic effect mechanism of main components; our results will clarify the main active compounds and anti-fibrosis MOA of FZHY in vitro and in vivo based on the influence in pathomechanism between LESCs injury and HSCs activation. Our research will promote FZHY internationalization.