基于PPARγ通路的A型原花青素肠道菌群代谢物抗动脉粥样硬化作用与机制研究

项目名称： 基于PPARγ通路的A型原花青素肠道菌群代谢物抗动脉粥样硬化作用与机制研究

项目编号： No.31471705

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 杨瑞丽

作者单位： 华南农业大学

项目金额： 70万元

中文摘要： 荔枝果皮A型原花青素具有极低的吸收率和显著的抗动脉粥样硬化（AS）活性。项目前期的研究表明，荔枝果皮A型原花青素抗AS活性可能与其肠道菌群代谢物有关。为明确肠道菌群代谢物对A型原花青素抗AS活性的作用与机制，本项目拟采用ox-LDL 刺激的巨噬细胞泡沫化模型，筛选确定其代谢产物的主活性组分，采用HPLC/MS、NMR等方法表征其化学结构；分析主活性产物对ox-LDL刺激的巨噬细胞PPARγ活化的影响，探讨细胞内与胆固醇逆向转运及炎症相关的关键基因表达和蛋白水平的变化；结合比较分析A型原花青素对正常与缺失肠道菌群ApoE-/-小鼠的动脉粥样硬化斑块形成、血浆和尿液中其代谢物HPLC谱的差异，以及PPARγ与其下游关键基因表达的变化，揭示以荔枝果皮为代表来源的A型原花青素肠道菌群代谢物抗AS的作用及分子机制。研究结果将丰富原花青素抗AS的理论基础，为特色植物天然产物的开发应用提供科学依据。

中文关键词： A型原花青素；肠道菌群代谢物；动脉粥样硬化；过氧化物酶体增殖物激活受体γ

英文摘要： A-type procyanidins of litchi fruit pericarp (LFP) with strikingly low absorptivity can prevent atherosclerosis (AS). We found that the function might be attributed in part to the metabolites of A-type procyanidins by gut microflora. Therefore, the active metabolites of procyanidin A2 and A-type procyanidin trimer from LFP by the gut microflora will be found according to the inhibitory activity on macrophage-to-foam cell transformation in vitro. Then, the active metabolites will be indentified with HPLC/MS and NMR. The possible effects and mechanism of the active metabolites will be explored in macrophage foam cells based on the signal pathway of PPARγ and the mRNA and protein expression of key genes in the reverse cholesterol transport and inflammation. In order to understand the anti-atherogenic effect of the metabolites of A-type procyanidins by gut microflora, the normal and germ-free ApoE-/- mice will be fed with A-type procyanidins from LFP. The atherosclerotic plaques and PPARγ-signaling pathway will be investigated. The microbial metabolites in plasma and urine will also be compared by HPLC analysis. The anti-atherogenic effect of microbial metabolites of A-type procyanidins and the molecular mechanism of activating PPARγ-signaling pathway will be clarified. The research will enrich the theoretical basis of AS-preventing effects of procyanidins, and provide the scientific basis for the development and application of natural plant products.

英文关键词： A-type procyanidins;microbial metabolites;atherosclerosis;PPARγ