GLP-1对阿尔茨海默病生物节律紊乱的调节研究

项目名称： GLP-1对阿尔茨海默病生物节律紊乱的调节研究

项目编号： No.81471343

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： 王晓晖

作者单位： 山西医科大学

项目金额： 70万元

中文摘要： 基于阿尔茨海默病（AD）与Ⅱ型糖尿病（T2DM）在发病上的相似性，我们的前期研究证明T2DM治疗性药物胰高血糖素样肽1（GLP-1）能够改善AD大鼠的学习记忆，并揭示了部分神经保护作用机理。结合AD患者早期出现的生物节律紊乱现象，我们设想GLP-1通过调节AD生物节律紊乱来发挥神经保护作用。本研究将采用动物跑轮行为学测试，观察在GLP-1作用下，小鼠在12：12LD（12小时开灯，12小时灭灯，光暗循环）和DD（持续黑暗）环境下生物节律的改变情况；通过离体细胞培养探讨节律性调控过程中cAMP和CREB的表达，观察神经细胞生长和凋亡情况，进一步采用实时定量PCR技术阐明生物钟基因节律变化，应用RNA干扰技术和基因过表达技术在细胞水平和在体水平研究GLP-1在生物节律调控过程中的重要性，从而为GLP-1参与调节AD生物节律紊乱和可能机制提供实验证据，为预防和治疗AD提供更合理的策略。

中文关键词： 胰高血糖素样肽1；阿尔茨海默病；生物节律

英文摘要： Based on the similarity in the pathogenesis of Type Ⅱ diabetes (T2DM) and Alzheimer disease (AD), our previous studies have proved that T2DM therapeutic drug glucagon-like peptide-1 (GLP-1) played a neuroprotective role through improving learning and memory function, and revealed part of the mechanism. Combined with the phenomenon that early AD patients appear biorhythm disorder，we assume that GLP-1 play a neuroprotective role in regulating the biorhythm disorder of AD. The study will observe the change of biorhythm in the process of GLP-1' neuroprotection through the mice' running wheel behavioral test in 12:12 LD (12 h-light : 12 h-dark cycle) and DD (constant darkness), investigate the expression of cAMP and CREB, observe the growth and apoptosis of neurons in the process of rhythmic regulation using cultured cells. Furthermore, we will clarify the change of circadian clock genes using real-time quantitative PCR and the importance of GLP-1 in regulating the biorhythms at the level of in vitro and in vivo using RNA interference and gene over-expression technology. The study will provide experimental evidence for GLP-1 involved in the regulation of biorhythm disorder of AD and possible mechanism in the process of neuroprotection. Simultaneously，the study will provide more reasonable strategy for the prevention and treatment of AD.

英文关键词： GLP-1;Alzheimer disease;Biorhythm