白藜芦醇/β-胡萝卜素调控肝细胞生物钟基因的作用与机制

生物钟基因是大脑中枢及外周组织细胞生物节律的基础，其表达紊乱容易引发多种慢性疾病，因此研究如何有效调控生物钟基因对促进机体健康具有重要意义。近期研究表明食物组分可有效调控生物钟尤其是外周生物钟信号，其中蛋白质、葡萄糖、维生素等营养物质为目前关注的热点，而大多数食物中同时富含多酚及类胡萝卜素类功能性因子，它们是否也对生物钟信号产生影响，目前鲜有报道。本项目以多酚和类胡萝卜素的代表性功能因子白藜芦醇和β-胡萝卜素为研究对象，以肝细胞生物钟基因为靶点，通过体内外实验分析功能因子对生物钟正负调控元件Clock/Bmal1及Per2表达的影响，探讨功能因子作用下PI3k/Akt及MAPK信号通路与生物钟基因的应答关系，并进一步阐明生物钟信号在功能因子促进肝细胞合成糖原中的作用。研究结果力争为丰富食物组分调控生物钟基因的深入研究提供新依据。

The clock genes are the base of biological rhythm in the brain central and peripheral tissue, disordering expression of which easily lead to many chronic diseases. Therefore, studies on how to control clock genes effectively are of great significance to promote health. Recent studies have shown that clock genes especially peripheral clock signal can be regulated effectively by food components. Protein, glucose, vitamins and other nutrients are hotspots at present. However, it has been rarely reported whether functional factors such as polyphenols and carotenoids which also exist in foods could have effects on clock gene signals. Taking clock genes in liver cell as a target, this project studies resveratrol and beta-carotene which are representative of polyphenols and carotenoids, analyzes the effects of functional factors on the expressions of positive and negative regulatory elements Clock/Bmal1 and Per2 in vivo and in vitro, investigates the response relationships between PI3k/Akt and MAPK signaling pathways and the biological clock genes, and further elucidates the role of clock genes signals on promoting glucose synthesis in liver cells. The results of the research will provide a new gist for further studies on the regulation of food components on clock genes.