基于UPR分子伴侣途径的葡萄皮多酚类物质延缓RPE衰老保护视觉功能的机制研究

项目名称： 基于UPR分子伴侣途径的葡萄皮多酚类物质延缓RPE衰老保护视觉功能的机制研究

项目编号： No.31271843

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 孙向军

作者单位： 上海交通大学

项目金额： 81万元

中文摘要： 视网膜色素上皮细胞（RPE）衰老是视觉功能老化的关键因素之一，课题组研究发现葡萄皮多酚能够抑制衰老的RPE发生凋亡，提示葡萄皮多酚可能具有延缓RPE衰老的作用，分子机制尚待探讨。RPE衰老的机制与未折叠蛋白反应（unfold protein response，UPR ）分子伴侣表达下调有关，我们前期研究表明葡萄皮多酚上调UPR关键分子伴侣GRP78的表达，分析可能通过调控GRP78等UPR分子伴侣表达延缓RPE细胞衰老。本课题旨在这些发现的基础上，明确葡萄皮多酚调控UPR关键分子伴侣表达与延缓RPE衰老之间的关系，揭示葡萄皮多酚通过调控UPR延缓RPE 衰老的分子机制，并且探讨葡萄皮主要多酚类物质之间的协同作用。本项目将为通过膳食营养抑制RPE衰老病变提供理论依据，为通过食品设计延缓视觉功能老化提供新思路

中文关键词： 葡萄多酚类物质；视网膜素色上皮细胞；脂褐素；氧化应激；凋亡

英文摘要： Retinal pigment epithelium (RPE) senescence is the main cause of age-related macular degeneration. We found that grape skin polyphenols prevent senile RPE from apotosis, suggesting their anti-ageing effect on RPE, the molecular mechanism remains unclear. The pathogenesis of senile RPE can be related to upregulating expression of unfold protein response (UPR) molecular chaperones. Our recent study showed that grape skin polyphenols upregulate expression of GRP78 which serves as a UPR molecular chaperone. It is reasonable to suppose that grape skin polyphenols exhibit anti-ageing effect on RPE by mediating GRP78 expression. In present study, we'll clarify whether the anti-ageing effect on RPE of grape skin polyphenols is related to upregulating expression of GRP78, reveal molecular mechanism by which grape skin polyphenols mediate expression of UPR molecular chaperones to exhibit anti-ageing effect on RPE, and investigate synergy of main polyphenol components. The project will provide fundamental basis for anti-ageing efficacy on RPE via dietary supplement, and show new idea of food design for inhibiting age-agerelated macular degeneration

英文关键词： grape polyphenols；retinal pigment epithelium；lipofuscin；oxidative stress；apoptosis