四种多酚类物质改善AD记忆的协同作用及对Aβ转运调节及NF-κB炎性反应抑制机制研究

项目名称： 四种多酚类物质改善AD记忆的协同作用及对Aβ转运调节及NF-κB炎性反应抑制机制研究

项目编号： No.81472984

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 赵海峰

作者单位： 山西医科大学

项目金额： 75万元

中文摘要： 大豆异黄酮、白藜芦醇、茶多酚、花青素改善AD记忆的协同作用及机制仍未阐明。Aβ的毒性作用是AD病理的中心环节，其清除转运功能障碍会过度激活胶质细胞，启动抗原呈递过程，诱发炎症反应。NF-κB 介导的炎性抑制成为AD防治的重要靶点。 本项目拟从人群、动物、细胞三个层面，聚焦：1.利用食物频率法结合24小时膳食回顾法对正常老龄化、MCI及AD的膳食中四种多酚类摄入量的比较； Meta分析其对记忆的单独作用及协同作用。 2.建立AD模型，利用正交设计的不同配伍干预，检测LTP； Aβ通过血脑屏障的外流及内向转运； NF-κB的核转位及活性； NF-κB上、下游因子的表达。3. 通过胶质细胞的培养，检测不同配伍对Aβ的直接吞噬作用以及胶质细胞对该作用的调节。验证四种多酚类物质的协同效应-Aβ转运调节-抑制胶质细胞激活-减少NF-κB介导的炎性反应-改善记忆这一假设，为AD的有效防治提供新思路。

中文关键词： 多酚类；阿尔茨海默病；记忆；淀粉样蛋白；核因子

英文摘要： Soy isoflavones, resveratrol, tea polyphenols and anthocyanins can all improve memory in Alzheimer's disease (AD). However, the synergies and mechanisms are not yet clarified. The deposit of Aβ is the major pathogen in AD, and the transporter dysfunction of it will excessively activate glial cells. Furthermore, inflammation reaction will be induced. Inhibition of NF-κB-mediated inflammatory has become an important target for the prevention and treatment of AD. The project intends to study focus on people, animals and cell levels, respectively. 1. Intake of the four polyphenols will be investigated in aging, MCI and AD population by food frequency questionnaire combines with dietary recall method. In addition, individual and synergistic effects of the four polyphenols will be analyzed by Meta analyzed. 2. Long term potentiation (LTP), Aβ transport through the blood brain barrier and NF-κB mediated inflammatory reaction will be tested at the end of the compatibility intervention by orthogonal design in AD model. 3. The directly scavenging effect of four polyphenols on Aβ and the regulation of glial cells. 'Synergistic effects of the four polyphenols- Aβ transport regulation- inhibiting glial cell activation- reduce the inflammatory response mediated by NF-κB- improve memory' will be verified and new ideas for the prevention and treatment of AD will be provided.

英文关键词： polyphenol;Alzheimer's disease;memory;Amyloid protein;NF-κB