皮肤光老化和细胞光损伤中的胆绿素代谢变化和外源性胆绿素基于Nrf2/ARE信号通路的保护作用机制研究

项目名称： 皮肤光老化和细胞光损伤中的胆绿素代谢变化和外源性胆绿素基于Nrf2/ARE信号通路的保护作用机制研究

项目编号： No.81502706

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 马良娟

作者单位： 哈尔滨医科大学

项目金额： 18万元

中文摘要： 紫外线照射诱发的氧化应激反应和细胞信号分子的激活是皮肤光老化发生的重要内源性机制。胆绿素（BV）及其代谢产物在许多疾病中发挥着抗氧化、抗炎和对信号分子的调节作用。我们前期的研究表明外源性BV对中波紫外线（UVB）诱导的皮肤慢性光损伤具有保护作用。本项目以此为基础，首先研究BV在光老化动物模型中的代谢变化和外源性BV对光老化的保护能力，然后通过建立光损伤细胞模型并利用基因转染及相关分子生物学技术，观察BV在细胞水平的代谢变化和对氧化应激及炎症反应的影响。联合观察外源性BV对光老化UVA途径和UVB旁分泌途径的影响，检测外源性BV对核转录因子Nrf2及其下游靶基因ARE基因和蛋白表达的影响，深入研究BV拮抗光老化的抗氧化机制。本项目将首次阐明BV在光老化发病机制中的作用，并为光老化的防治提供新的治疗策略和奠定理论基础。

中文关键词： 紫外线照射；皮肤光老化；细胞光损伤；胆绿素

英文摘要： Oxidative stress and cell signaling molecules activation induced by ultraviolet(UV) are the important endogenous mechanism in skin photo-aging. The research has proved that biliverdin (BV) and its metabolites have the anti-oxidant and anti-inflammatory effects, and involves in the regulation of signaling pathways in many diseases. Our previous study validated that exogenous BV has a protective effect on UVB-induced skin chronic photo-damage. Along with these observations，we will observe the metabolic changes of BV and protection capabilities of exogenous BV in photo-aging animal model. Then, we will use UV- damage cell model to observe the metabolic changes of BV at the cell level and the effect of BV on oxidative stress and inflammatory reaction by the gene transfection and related techniques of molecular biology. And, we will observe the role of exogenous BV in photo-aging of UVA pathway and UVB paracrine pathway. Furthmore, we look forward to focus on the impact of exogenous BV on the expression of gene and protein of Nrf2 and its effect downstream target gene ARE in photo-damage. So we will thoroughly investigate the mechanism of BV against photoaging on oxidative stress. The topic explores for the first time that the effect of BV in mechanism of skin photo-aging and cell photo-damage, and provide a new therapeutic strategie and a theoretical foundation for photoaging.

英文关键词： ultraviolet irradiation; photo-aging;cell photo-damage;biliverdin