Snail蛋白在酒精性肝纤维化中的关键作用及清肝活血方调控机制研究

项目名称： Snail蛋白在酒精性肝纤维化中的关键作用及清肝活血方调控机制研究

项目编号： No.81202979

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 吴涛

作者单位： 上海中医药大学

项目金额： 23万元

中文摘要： 课题组基于临床流行病学和数据挖掘技术，提出"湿热瘀血"为酒精性肝纤维化的核心病机，临床及实验研究并证实清肝活血方在改善酒精性肝损伤方面有良好的效果。前期已完成的国家自然基金项目发现，清肝活血方通过干预内毒素-库普弗细胞信号途径改善酒精性肝损伤。进一步研究发现，还可通过调控uPA纤溶途径发挥防治酒精性肝纤维化的作用。新近研究显示，Snail是调节纤维形成的重要核转录因子，其转录异常直接影响肝纤维化中上皮间质转化的进程，而上皮间质转化是导致肝纤维化的重要途径。本课题拟制备酒精性肝纤维化大鼠模型，并结合RNAi 致Snail-/-肝细胞上皮间质转化模型，应用病理学和分子生物学等实验技术，从基因和蛋白水平探讨清肝活血方对Snail-上皮间质转化信号通路作用靶点及强度，以期阐明Snail 蛋白在酒精性肝纤维化中的作用以及清肝活血方调控机制，这对促进中医药防治酒精性肝纤维化有重要的基础和应用价值。

中文关键词： 酒精性肝纤维化；清肝活血方；上皮间质转化；Snail；TGF-β1/Smad信号通路

英文摘要： The group put forward "damp heat and blood stasis" as the core pathogenesis of alcoholic liver fibrosis based on clinical epidemiology and data mining technology. Clinical and experimental studies have shown that Qinggan Huoxue Recipe can improve the alcohol-induced liver injury. The completed national natural fund project has discovered that, Qinggan Huoxue recipe improved alcohol-induced liver injury through the intervention of endotoxin-Kupffer cell signaling pathways. Further research found that, Qinggan Huoxue recipe relieved alcoholic liver fibrosis through regulation of uPA pathways. Recent research has shown, Snail is a nuclear transcription factor, whose abnormal transcription directly affects epithelial-mesenchymal transition process in liver fibrosis. In this project, we would apply alcoholic liver fibrosis rat model and hepatocyte epithelial mesenchymal transition model to elucidate the targets and strength of Qinggan Huoxue Recipe on Snail-epithelium mesenchymal transition signal pathway, and clarify the important role of Snail from the level of gene and protein, which is of important basic and applied values to promote the prevention and treatment of alcoholic liver fibrosis of traditional Chinese medicine.

英文关键词： Alcoholic liver fibrosis；QGHXR；Epithelial-to-Mesenchymal Transition；Snail；TGF-β1/Smads signal pathway