中文摘要：

通过Toll样受体4（TLR4）抑制剂表没食子儿茶素没食子酸酯（EGCG）对TLR4途径的抑制，研究apoE^-/-小鼠TLR4及多种炎症因子的表达和动脉粥样硬化病变程度的改变，以探讨TLR4途径在动脉粥样硬化病变发生中的作用．5周龄雄性apoE^-/-小鼠50只，随机分成4组：基础饮食组对照组（n=12）、高脂饮食组对照组n=12）、基础饮食＋EGCG组n=13）、高脂饮食＋EGCG组n=131．给药14周后处死动物，从主动脉根部连续冰冻切片，油红O染色观察主动脉窦处动脉粥样硬化（As）斑块面积，定量分析主动脉粥样硬化斑块大小及占管腔的面积百分比，采用Real time-PCR检测主动脉TLR4mRNA和CD14mRNA的表达，蛋白质印迹检测TLR4和CD14蛋白表达，ELISA检测小鼠血清中单核细胞趋化蛋白-1（MCP-1），肿瘤坏死因子-α（TNF—α）浓度．研究结果提示：EGCG显著减轻apoE^-/-主动脉窦部的动脉粥样硬化病变，高脂对照组的主动脉窦AS斑块面积为（2．37±0．08）mm^2，高脂饲料＋EGCG组的主动脉窦AS斑块的面积为（1．05±0．13）mm^2，EGCG组小鼠主动脉窦粥样斑块面积比相应对照组明显减少（P〈0．05），高脂饮食＋EGCG组小鼠TLR4蛋白表达显著降低（P〈0．05），MCP—1，TNF—α的含量减少，与高脂饮食对照组相比差异有显著性（P〈0．05）．TLR4信号转导途径在高脂所致的AS发生当中有着重要作用，该信号途径的激活至少是AS发生当中的一个重要环节．

英文摘要：

It is known that （-）-Epigallocatechin-3-gallate （EGCG） is the inhibitor of TLR4 signaling pathway activation. To investigate a possible role of TLR4 signaling pathway in the development of atherosclerosis, the effects of EGCG on the development of atherosclerosis, the expression of TLR4 and inflammatory cytokine production in apoE^-/- mice was investigated. Fifty male apoE^-/- mice （5wk old） were divided into four groups： basic diet group （control group）, high-fat diet group （control group）, EGCG ＋ basic diet group （EGCG group）, and high-fat diet ＋ EGCG group （EGCG group）. EGCG （10 mg/kg） was injected intraperitoneally every day. Areas of aortic plaque areas were measured by oil red O staining. Western blot was used to detect the expression of TLR4 and CD14 in mouse aorta. The expression of TLR4 mRNA and CD14 mRNA were detected by Real-time PCR. Serum concentrations of MCP-1 and TNF-α were determined with ELISA. Compared with high-fat diet group, EGCG groups showed marked decreases in aortic atherosclerosis （P 〈 0.05）, concomitantly with significant decreases in levels of the expression of TLR4, TNF-α and MCP-1. The mean lesion area was （2.37 ±0.08） mm^2 in the high-fat diet ＋ EGCG group, whereas the atherosclerotic lesion was only （1.05 ± 0.13） mm^2 in the high-fat diet ＋ EGCG group. The TLR4 expression was obviously higher in high-fat diet group than that in other groups （P 〈 0.05）. Compared with high-diet group, the serum concentrations of MCP-1 and TNF-α were significantly decreased in EGCG groups （P 〈 0.05）. These results suggest that TLR4 signaling pathway may play an important role in the development of atherosclerosis in apoE^-/- mice induced by high-fat diet.