绿茶多酚EGCG通过67LR途径稳定动脉粥样硬化斑块的作用及其相关分子机制研究

冠心病是严重危害人类健康的重要疾病，稳定易损的粥样硬化斑块对于急性冠脉综合征的防治具有极其重要的临床意义。绿茶是我国民众的主要日常饮品，我们先前的研究表明饮用绿茶可显著降低冠心病的发病风险，但具体机制目前尚不明确。作为绿茶多酚的主要成分，EGCG具有各种生物及药理学效应，本课题组进一步发现，EGCG不仅可以通过作用于人脐静脉内皮细胞67LR抑制TNF-α诱导的MCP-1表达，而且能够抑制单核细胞与内皮细胞的黏附。此外，我们的预实验已发现EGCG具有抑制EMMPRIN及MMPs分泌的功能。因此，我们推测EGCG可能具有稳定动脉粥样硬化斑块的作用。本项目旨在通过动物、细胞及分子水平系列研究明确EGCG是否通过67LR抑制巨噬细胞EMMPRIN及MMPs的表达，从而发挥增强动脉粥样硬化斑块稳定性的作用，并深入探讨相关作用机制。研究结果将为绿茶防治冠心病提供新的思路，具有重要的社会经济学效益。

Coronary artery disease (CAD) is still the most common cause of death worldwide. It is very important to make atherosclerotic plaque stabilization to prevent the onset of acute coronary syndrome; this has an extremely important clinical implications. Our previous studies have reported that daily consumption of green tea is associated with a reduced risk of CAD. Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, displays a variety of pharmacological properties and recently received attention as a prospective dietary intervention in CAD. Our pilot study has identified that EGCG was able to inhibit tumor necrosis factor-α (TNF-α)-induced production of monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs); EGCG potently inhibited monocyte adhesion to activated HUVECs. Our further study also found that EGCG was able to inhibit the production of EMMPRIN and MMPs. Therefore, we hypothesis that EGCG can stabilize atherosclerotic plaques; it could be the first study to show that the 67-kD laminin receptor (67LR) was involved in EGCG-mediated suppression of EMMPRIN and MMPs generation. Our results will demonstrate that EGCG might be a possible medicine for CAD prevention and treatment.