PGC-1α/UCP2信号通路在飞燕草素抑制血管内皮细胞线粒体损伤中的作用

项目名称： PGC-1α/UCP2信号通路在飞燕草素抑制血管内皮细胞线粒体损伤中的作用

项目编号： No.81202202

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： 陈春烨

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 本实验室前期研究发现，存在于多种天然有色植物中的飞燕草素（Dpg）能显著抑制血管内皮细胞功能障碍，对动脉粥样硬化（AS）可能具有潜在的防治作用，但分子机制尚不明确。线粒体活性氧（ROS）增加是导致内皮功能障碍的重要诱因，其生成主要受线粒体解偶联蛋白（UCP2）调控，而UCP2的表达及活性与过氧化物酶增殖激活受体辅助活化因子1( PGC-1α)密切相关。本项目拟在前期研究基础上，围绕内皮细胞线粒体损伤这一AS发生的早期事件，运用激光共聚焦、免疫印迹、实时PCR、荧光素酶报告基因、干扰RNA等方法，针对线粒体活性氧生成机制，从PGC-1α活性调节、UCP2表达及活性、电子传递链氧化磷酸化、ROS生成等方面阐明PGC-1α/UCP2信号通路在Dpg抑制内皮细胞线粒体损伤中的作用机制。该项目的突出意义旨在深入揭示飞燕草素抗AS作用的分子机制，为寻找AS防治的新策略提供理论依据。

中文关键词： 飞燕草素；内皮功能障碍；线粒体；自噬；活性氧

英文摘要： Delphinidin-3-glucoside belong to the widespread class of phenolic compounds and have been reported to exert beneficial properties against cardiovascular diseases due to their multitude biological activities. Our previous studies have shown that delphinidin-3-glucoside may have inhibitive effects on oxidative-stress-induced vascular endothelial dysfunction. However, the mechanism has not been elucidated. Excessive production of reactive oxygen species (ROS) in the mitochondria plays a major role in the development of endothelial dysfunction. And the ROS production is regulated by the uncoupling protein 2 (UCP2), which is activated by the peroxisome proliferator activated receptor (PPAR)γ coactivator 1-α (PGC-1α). In this study, we aim to explore the role of PGC-1α/UCP2/ROS signaling pathway in the inhibition of endothelial mitochondrial dysfunction by anthocyanins. qRT-pcr, western blotting analysis, Laser Confocal Microscope, reporter gene and RNAi were applied to measure the activity of PGC-1α, the expression and activity of UCP2, oxidative phosphorylation of the lectron transfer chain, and the ROS production, The findings may provide a basis for the design of potent antiatherosclerotic agents that will have therapeutic potential in the prevention of AS.

英文关键词： delphinidin-3-glucoside；endothelial dysfunction；mitochondria；autophagy；ROS