茵陈蒿汤调控Notch信号通路影响库普弗细胞活化的效应机制研究

More and more research focused on Notch signaling pathways involving in macrophage differentiation and its function. However, the relationship between Notch signaling pathway and activation of kupffer cell has not known. The role of Notch signaling in liver fibrosis is not clear yet. Based on significant efficacy of Yin-chen-hao Decoction of significant inhibition of inflammation and abnormal Notch signaling pathways in liver fibrosis model induced by DMN, We put forward the hypothesis that Yin-chen-hao Decoction regulates Notch signaling pathways and inhibits activation of kupffer cell to inhibit liver fibrosis. We will employ primary kupffer cell, RAW264.7 cell line and liver fibrosis model induced by DMN, to investigate the relationship between Notch signaling pathway and macrophage differentiation and its function, explore the anti-inflammation and anti-fibrosis mechanism of Yin-chen-hao Decoction. In agreement with the in vitro and in vivo data, we will show that Notch pathway selectively mediate fibrogenic properties of kupffer cell and Yin-chen-hao Decoction regulates the relationship between Notch pathway and kuppfer cell to inhibit liver fibrosis. The results will represent a novel therapeutic target to liver fibrosis also.

库普弗细胞作为肝内的巨噬细胞，在肝纤维化形成与逆转过程中所具有的"双刃剑"作用日益受到重视。Notch信号通路对巨噬细胞分化和功能影响的研究已较深入，但迄今尚未见Notch调控库普弗细胞的研究报道。本项目基于前期研究DMN肝纤维化模型存在显著的炎症反应和Notch信号通路异常，茵陈蒿汤具有调控Notch信号通路、抑制库普弗细胞活化及显著的抗肝纤维化作用的研究结果，提出"茵陈蒿汤可能是通过调控Notch信号通路影响库普弗细胞活化从而抗肝纤维化作用"的假说。项目以细胞与DMN大鼠肝纤维化模型为对象，以茵陈蒿汤及成分/配伍干预，研究在肝纤维化中Notch信号通路、库普弗细胞活化与肝纤维化发生、发展及转归的关系，揭示Notch信号调控库普弗细胞活化的炎症反应导致肝纤维化的发生、发展及茵陈蒿汤的效应机制，促进茵陈蒿汤的应用发展。

本项目基于前期研究DMN肝纤维化模型存在显著的炎症反应和Notch信号通路异常，茵陈蒿汤具有调控Notch信号通路、抑制库普弗细胞活化及显著的抗肝纤维化作用的研究结果，提出"茵陈蒿汤可能是通过调控Notch信号通路影响库普弗细胞活化从而抗肝纤维化作用"的假说。项目以细胞与DMN大鼠肝纤维化模型为对象，以茵陈蒿汤及成分/配伍干预，研究在肝纤维化中Notch信号通路、普弗细胞活化与肝纤维化发生、发展及转归的关系，揭示了库普弗细胞活化的炎症反应导致肝纤维化的发生、发展及Notch、JNK与NF-kB等通路的影响，并阐明了茵陈蒿汤及其主要成分大黄酸和大黄素的的效应机制，促进茵陈蒿汤的应用发展。.发表学术论文17篇，SCI收录6篇，影响因子18.1分；会议论文9篇；培养研究生5名，其中三名研究生获得国家奖学金、1名研究生获得上海市优秀毕业生，2人获得上海中医药大学优秀学位论文二、三等奖。获得授权专利1项，奖励1项。