EGCG通过Notch调节炎症的分子机制

项目名称： EGCG通过Notch调节炎症的分子机制

项目编号： No.31460392

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 王宣军

作者单位： 云南农业大学

项目金额： 52万元

中文摘要： 炎症是糖尿病、肿瘤、心血管疾病等多种疾病的诱发或促进因素。绿茶中的EGCG有降低炎症反应的效果。国外报告EGCG在小鼠巨噬细胞模型上通过层粘连蛋白受体LR发挥抑制炎症效应。Notch信号途径也参与炎症反应的调节。前期研究发现：1.在人巨噬细胞炎症模型中封闭LR对EGCG的炎症抑制效果没有影响；2.EGCG能够快速抑制Notch信号；3.RNA干扰降低Notch的直接效应转录因子CSL的表达能够消除EGCG的炎症抑制效应。在此基础上，本项目拟以人巨噬细胞炎症反应模型为研究对象，研究下列内容：1.EGCG抑制Notch信号的作用方式；2.Notch亚型在EGCG抑制炎症反应中的作用差异。本项目的研究成果可以阐明EGCG抑制Notch进而抑制炎症反应的分子机理。研究结果将为人们通过科学地饮茶进行炎症相关疾病的防治提供依据，也有助于人们深入了解细胞、机体与食物成份的相互作用及其机制。

中文关键词： 茶多酚；分子机制；转录因子；信号通路；抗肿瘤

英文摘要： Inflammatory may play decisive roles at different stages of the development of the diabetes, tumor and cardiovascular disease. The (-)-Epigallocatechin gallate(EGCG), contains in the green tea, can attenuate the inflammatory responses effectively. The foreign reseaechers had reported the 67KD laminin receptor(LR) is the target of EGCG for the effect of inflammation reducing in mice macrophage model. In our experiments performed on the human macrophage model for the inflammation response, the inflammatory attenuating effect of EGCG didn't decrease after the LR blocked with the antibody which has been declared effectively in the LR blocking. These facts suggested there have unknown new inflammatory reducing receptor on the cell membrane for the EGCG except the 67LR. Recent years,Notch signaling pathway had been found playing essential role in the regulation of inflammation response.The ongoing experiments of this project have found: 1. The Notch signal can be inhibited rapidly by treat the cells with EGCG; 2. The effects of the attenuating inflammation by the EGCG was erased if the direct effective transcripe factor for the Notch signal pathway, CSL, was decreased by the siRNA. Basis on these fact, this project will design and perform experiments below on the human inflammation response macrophage model: 1. To clear the mechanisms of the Notch inhibited by the EGCG; 2. To reveal the function difference between 4 subtypes of Notch in the processing of inflammation reducing effects of EGCG. The achievements of this project will clarify the Notch related molecular mechanism in inflammation attenuate of EGCG, also provide evidences that prevent the inflammation related disease through the tea drinking. This project will show evidence for the interaction and the mechanisms between the human body and the compounds contains in the food.

英文关键词： Tea polyphenol;molecular mechanism;transcription factor;signal pathway;anti-tumor