基于TGF-β/Smad 信号通路的莪术醋制抗肝纤维化代谢组学研究

项目名称： 基于TGF-β/Smad 信号通路的莪术醋制抗肝纤维化代谢组学研究

项目编号： No.81473349

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 毛春芹

作者单位： 南京中医药大学

项目金额： 76万元

中文摘要： 中药炮制是中医临床辩证用药的特色，但指导饮片合理应用的炮制理论尚缺乏现代科学论据，成为制约中药现代化的瓶颈。莪术抗肝纤维化效应为临床验证，醋制后增强散瘀消积及抗肝纤维化作用，但醋制增效机制未见研究。肝纤维化是肝病发展为肝硬化或肝癌的必经阶段，是唯一可被逆转阶段。抗肝纤维化机制与信号通道及纤溶系统等关联密切。针对上述问题及前期研究基础，项目以HSC、信号通路、纤溶系统及代谢组学等为切入点，创新性地将LC-TOF/MS、PCR等前沿技术引入莪术醋制机制研究，探讨其对肝纤维化关键靶点的调控及代谢组分的动态变化。从分子表达、信号转导、代谢组学等环节系统研究，阐明莪术醋制是通过调控TGF-β/Smad信号通路，维持uPA-MMPs-PAI-1级联反应系统平衡，改变机体内源性靶标代谢组分及特异代谢通路而增强抗肝纤维化作用假说的科学内涵。为醋制莪术临床应用提供理论依据，也为中药炮制现代研究

中文关键词： 莪术；醋制；抗肝纤维化；TGF-β/Smad；信号通路；代谢组学

英文摘要： The processing theory of traditional chinese medicine(TCM) is the characteristic of Chinese clinical medicine ,but the theory that guide decoction pieces application of safe and effective is short of modern scientific argument，thus it had become the bottle neck of Modernization of TCM. Hepatic fibrosis, the mutual pathologic change and inevitable stage in the development of most kinds of chronic liver diseases into hepatic cirrhosis and even hepatic cancer, was an unique reversible stage. The key mechanism in treatment of hepatic fibrosis are closely connect with signal channel and fibrinolytic system. To the problems mentioned above and the early stage research of our project, we introduce advanced technologies, such as LC-TOF/MS, polymerase chain reaction(PCR) and so on, to theoretical research field of processing innovatively. We discuss the regulation function of vinegar processed Curcumae Rhizoma to liver fibrosis key targets and its dynamic change of endogenous metabolism component, with hepatic stellate cells(HSC）, fibrinolytic system, transforming growth factor-beta(TGF - β)/Smad pathway and metabolomics, etc as the breakthrough point, through the overall identification and target analysis. We will further discuss the mechanism of anti-hepatic fibrosis effect of Curcumae Rhizoma processed with vinegar from molecular expression、signal transduction and metabonomics. To charify scientific connotation of that Curcumae Rhizoma processed with vinegar played the anti-hepatic fibrosis role, through regulating the TGF-β/Smad signaling pathways, maintaining the system of urokinase-plasminogenactivator-matrix metalloproteinases- plasminogen activator inhibitor-1(uPA-MMPs-PAI-1) cascade reaction balance and changing endogenous metabolism of target components and specific metabolic pathways . We aimed to provide a theoretical basis for Clinical Science utilization of vinegar processed Curcumae Rhizoma, annotate the traditional theory of processing with modern scientific language and provide a demonstration for modern research of processing theory.

英文关键词： Curcumae Rhizoma;processed with vinegar;anti-hepatic fibrosis;TGF-β/Smad signal path;metabonomics