申请人证实7-二氟甲氧基-5,4'-二甲氧基金雀异黄素（DFMG）具有体内外抗动脉粥样硬化(AS)效应（专利号：ZL200710104389.4）,且新近发现DFMG降低氧化应激人主动脉内皮细胞TNF-R2磷酸化水平和下调TLR-4蛋白表达，但DFMG抗AS作用的分子调控机制仍未知。本项目拟在AS相关细胞(内皮细胞、血管平滑肌细胞和巨噬细胞)，针对TLR-4进行基因调控(沉默/过表达)，研究DFMG对TLR-4相关蛋白及其触发MyD88和TRIF依赖信号传导途径和这些信号传导调控细胞粘附和炎症因子分泌功能的影响；并在TLR-4基因敲除小鼠模型上，进一步验证DFMG对TLR-4信号传递相关的MyD88依赖性、TRIF依赖性途径的影响，探讨DFMG体内外抗AS作用的分子机制。研究结果有助于阐明DFMG调控TLR-4信号传导发挥抗AS作用的分子机制，为DFMG防治AS研究提供实验和理论依据。

It was proved that 7-Difluoromethyl-5,4'-dimethoxygenistein(DFMG) with Chinese Patent No.ZL200710104389.4 had the anti-atherosclerosis effect in vivo and in vitro by the applicant. We have found that DFMG could reduce the level of phosphorylated TNR receptor-2 and expression of TLR-4 protein in injured HAECs induced by oxidative stress, but the molecular mechnism by which modulate the anti-atherosclerosis effect still is unknown. In this research project, we will plan to explore the effect of DFMG on TLR4 asscociated proteins,TLR-4 MyD88-dependent signaling pathway, TLR4 TRIF-dependent signaling pathway and expression of inflammatory cytokines and adhesion molecules in the cultured human endothelial cells, macrophages and vascular smooth muscle cells by gene regulation of TLR-4;then, further validate the effect of DFMG on TLR-4 MyD88-dependent and TRIF-dependent signaling pathway in TLR-4 knockout mice.The findings of this research will reveal the detailed molecular mechanisms of DFMG by which regulate TLR-4 signal transduction against the atherosclerosis, which will provide a scientific basis to exploit and utilize DFMG in prevention and treatment of atherosclerosis in hunman.