miR-30d/eNOS信号通路在花色苷调节血管内皮舒张功能中的作用研究

血管内皮功能紊乱是动脉粥样硬化（AS）发生发展的始动因素和关键环节，花色苷类植物化学物可以通过改善血管内皮功能紊乱而发挥抗AS的作用，但其中的作用机制尚不明确。我们前期研究发现花色苷可通过激活内皮型一氧化氮合酶（eNOS）的活性增强高胆固醇血症患者血管内皮舒张功能，并使患者血浆miR-30d的表达显著下降，且采用生物信息学软件分析发现eNOS是miR-30d的靶基因；在此基础上，本项目拟在内皮细胞和离体动脉环观察miR-30d对eNOS表达以及血管内皮舒张功能的影响，并明确miR-30d在花色苷提高血管内皮舒张功能中的调控作用；然后在ApoE基因敲除小鼠中探讨miR-30d/eNOS途径在花色苷改善血管内皮舒张功能中的作用；同时，比较食物中最常见的两种花色苷的上述作用有无差异。研究将揭示花色苷改善血管内皮舒张功能的作用机制，并为miR-30d作为促进血管内皮舒张功能的干预靶点提供理论基础。

Vascular endothelial dysfunction is the initial factor and the key step in the initiation and development of atherosclerosis (AS). Anthocyanins, a type of phytochemical compounds, have been identified to have anti-atherosclerotic property by regulating vascular endothelial dysfunction, however, the underlying mechanism is still unclear. Our previous study found that anthocyanins can enhance vacular endothelial dilatation function in hypercholesterol subjects by stimulating endothelial nitric oxide synthase (eNOS) activity, and decrease plasma microRNA-30d (miR-30d) expression. Then, we also found that eNOS is the target gene of miR-30d after analyzing by bioinformatics software. Therefore, we plan to explore the effect of miR-30d on eNOS expression and vacular endothelial dilatation function in endothelial cells and isolated aortic rings. Moreover, the relationship between miR-30d and anthocyanins' effect on the improvement of vacular endothelial dilatation function would be explored. Finally, the effect of miR-30d/eNOS pathway on anthocyanins-induced improvement of vacular endothelial dilatation function would be studied in ApoE gene knockout mice. Additionally, we would also examied whether there is a difference of the above bioactive function between the most two common anthocyanins in food. Our study would identify the underlying machanism of anthocyanins' effect on the improvement of vacular endothelial dilatation function, as well as provide theoretial foundation for miR-30d as a target to promote vascular endothelial dilatation function.