矢车菊素-3-O-葡萄糖苷肠道细菌代谢物原儿茶酸对巨噬细胞胆固醇逆向转运的影响及其机制研究

项目名称： 矢车菊素-3-O-葡萄糖苷肠道细菌代谢物原儿茶酸对巨噬细胞胆固醇逆向转运的影响及其机制研究

项目编号： No.81202196

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 王冬亮

作者单位： 中山大学

项目金额： 23万元

中文摘要： 大量的研究报道矢车菊素-3-O-葡萄糖苷（C3G）具有防治动脉粥样硬化（AS）的作用，但由于C3G吸收率非常低，血浆浓度很低，其发挥抗AS作用的活性形式及其机制尚不清楚，需要深入研究。我们初步发现C3G肠道细菌代谢物原儿茶酸（PCA）可提高ABCA1和ABCG1表达，促进巨噬泡沫细胞胆固醇外流，其效应与miR-10b表达负相关。在此基础上，本项目拟采用巨噬泡沫细胞模型，明确miR-10b特异性调控ABCA1和ABCG1表达介导了PCA促进胆固醇外流作用；然后，采用正常肠道菌群及肠道菌群缺失的ApoE-/-小鼠模型，验证PCA具有促进巨噬细胞胆固醇逆向转运（RCT）的作用，其机制涉及miR-10b-ABCA1/ABCG1通路，并且明确PCA为其原形C3G发挥促进巨噬细胞RCT效应的主要活性形式。本研究将为C3G防治AS和miR-10b作为促进巨噬细胞胆固醇外流的干预靶点提供理论依据。

中文关键词： 花色苷；肠道细菌；原儿茶酸；微小RNA；动脉粥样硬化

英文摘要： Although numerous studies had demonstrated that cyanidin-3-O-glucoside (C3G) possesses antiatherosclerotic property,the pharmacodynamic material basis and the underlysing mechanism remain unclear due to the very low absorption rate of C3G leading to a low plasma C3G concentration. Our recent findings revealed that protocatechuic acid (PCA), a gut microbiota of C3G, promoted cholesterol efflux from macrophage-derived foam cells arising from up-regulation of ABCA1 and ABCG1 expression, which was negatively associated with cellular miR-10b expression. Based on the above findings, we would firstly elucidate the specific role of miR-10b in the stimulatory effects of PCA on ABCA1/ABCG1 expression and cholesterol efflux capacity using macrophage-derived foam cells. Next,we would test the possibilities whether PCA promotes macrophage RCT and activates the miR-10b-ABCA1/ABCG1 pathway, as well as whether PCA is mainly responsible for the stimulatory effect of its precursor C3G on macrophage RCT using the normal gut microbiota and gut microbiota-deficient apolipoprotein-E knockout mouse models.Our study would provide theoretical foundation for the implication of anthocyanin in protecting against atherosclerosis,and identify miR-10b as a new target to promote cholesterol efflux from macrophages.

英文关键词： anthocyanin；gut microbiota；protocatechuic acid；microRNA；atheroscelrosis