基于NOX/ROS及Nrf2/ARE信号途径探讨绿原酸抗肝纤维化机制

项目名称： 基于NOX/ROS及Nrf2/ARE信号途径探讨绿原酸抗肝纤维化机制

项目编号： No.81200310

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 史海涛

作者单位： 西安交通大学

项目金额： 23万元

中文摘要： 流行病学研究表明咖啡饮用可降低肝纤维化的发病风险，但何种成分发挥作用尚不清楚，绿原酸是咖啡中含量丰富的的一种多酚，具有强大的抗氧化活性。本课题组前期研究表明绿原酸可减轻四氯化碳诱导的肝纤维化，但具体机制尚不完全清楚。NOX/ROS氧化通路和Nrf2/ARE抗氧化通路在肝纤维化发生发展中具有重要的作用。本研究拟采用四氯化碳及胆管结扎法建立两种肝纤维化模型，从组织水平、分子水平评估绿原酸的治疗作用，并检测其对肝脏氧化应激状态的影响，体外原代培养大鼠肝星状细胞研究绿原酸对NOX/ROS通路的影响，体外原代培养肝细胞研究绿原酸对Nrf2/ARE通路的影响。本课题以氧化应激为切入点，从整体、细胞、分子水平探讨绿原酸抗肝纤维化机制，为其临床应用提供理论及实验依据。

中文关键词： 肝纤维化；绿原酸；活性氧；抗氧化；

英文摘要： Recent epidemic studies suggest that coffee consumption may reduce the risk of hepatic fibrosis. However, there are many components in coffee and which one being responsible for the protective effect is not clear. Chlorogenic acid(CGA), rich in coffee drinks, is a kind of polyphenol and exerts antioxidant activities. We previously showed CGA could improve CCl4 induced hepatic fiboriss in rats，but the exact mechanism is not clear. NOX/ROS oxidative pathway and Nrf2/ARE antioxidative pathway have important roles in initiation and progression of hepatic firbosis. We will evaluate the effect of CGA on liver fibrosis from histology and cell levels in bile duct ligation (BDL) and carbon tetrachloride (CCl4) models. We will also detect the effect of CGA on NOX/ROS pathway in primary rat hepatic stellate cell cultures, and the effect of CGA on Nrf2/ARE pathway in primary rat hepatocyte cultures. We study the effect of CGA on hepatic fibrosis at the level of organ-cell-molecule to provide theoretical and experimental evidence for its clinical application.

英文关键词： hepatic fibrosis；chlorogenic acid；reactive oxygen species；antioxidation；