杠板归对肝纤维化TGF-β1/Notch 信号通路负反馈作用及其谱效关系研究

项目名称： 杠板归对肝纤维化TGF-β1/Notch 信号通路负反馈作用及其谱效关系研究

项目编号： No.81460602

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 高雅

作者单位： 桂林医学院

项目金额： 47万元

中文摘要： 杠板归在临床上常用来治疗肝病并取得良好疗效，课题组发现杠板归可有效防治二甲基亚硝胺诱导的大鼠肝纤维化，并对其肝组织中TGF-β1的表达有显著抑制作用。TGF-β1是导致上皮间质转化（EMT）最强的细胞因子，EMT在纤维化发生中起到重要作用，Notch通路已被证实与EMT有关。因此，本研究在结合Notch通路与多器官纤维化相关性的基础上，应用中医异病同治 理论思想，通过研究TGF-β1/Notch信号通路参与肝纤维化发生发展的负反馈作用，来探讨杠板归抗肝纤维化的作用机制。 针对中药化学指纹图谱存在图谱与药效相脱节的问题，本课题拟以肝纤维化大鼠血清中TGF-β1为药效指标，运用血清药物学和色谱学的技术与方法, 通过HPLC-MS跟踪检测杠板归中的入血有效成分，建立HPLC药效指纹图谱，并用灰色关联度分析法，获得谱效数据之间的对应关系, 探究一种基于药效和化学成分相融合的质量评价方法。

中文关键词： 杠板归；肝纤维化；上皮间质转化（EMT）；TGF-β1/Notch；信号通路；谱效关系

英文摘要： Polygonum perfoliatum was used to treat liver disease and have achieved good effect in clinical , Our research group found Polygonum perfoliatum can control the rat liver fibrosis effectively,which caused by the DMN, and inhibited expression of TGF-β1 in liver tissue significantly. TGF-β1 is the strongest cytokines induced epithelial- mesenchymal transition (EMT).EMT play an important role in the occurrence of liver fibrosis , Notch signaling pathway has been confirmed related to EMT . Therefore, base on the Notch signaling pathway have correlated with multiple organ fibrosis and application of Chinese medicine theory,which is different diseases treated with the same method.By studying the TGF-β1/Notch signaling pathways have the negative feedback effect of liver fibrosis process to explore the antifibrotic mechanism of the Perfoliatum perfoliatum. For the problem of quality reserch of Traditional Chinese Medicine ,which fingerprits are seriousely out of joint with efficacy.The topic to serum TGF-β1 as pharmacodynamic index in live fibrosis rats . Using the techniques and methods of Serum Pharmacology and Chromatography .By HPLC-MS tracing and detecting the active ingredient into the blood of Perfoliatum perfoliatum to establishing the efficacy HPLC fingerprint .In addition,Using the gray correlation analysis method to obtain correspondence between spectral data and efficiency ,This study aim to set up a quality evaluation mehtod,which integrating chemical composition analysis and biological activity .

英文关键词： Polygonum perfoliatum L.;Hepatic fibrosis;epithelial-mesenchymal transitions;TGF-β1/Notch signaling pathway;spectrum-effect relationship