金思维提取物对3×Tg-AD转基因小鼠脑内蛋白质质量控制网络的影响

项目名称： 金思维提取物对3×Tg-AD转基因小鼠脑内蛋白质质量控制网络的影响

项目编号： No.81473518

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： 田金洲

作者单位： 北京中医药大学

项目金额： 75万元

中文摘要： 背景：β-淀粉样蛋白(Aβ)和过度磷酸化Tau蛋白(P-Tau) 的堆积是阿尔茨海默病（AD）的主要病理改变，这与蛋白质质量控制网络异常及蛋白折叠异常和降解受阻有关。前期临床研究发现，金思维提取物补肾化痰能够显著改善AD患者的认知症状。目的：评价补肾化痰法中药对3×Tg-AD转基因小鼠脑内分子伴侣蛋白、泛素-蛋白酶体和自吞噬-溶酶体系统的影响。方法：应用跳台实验和Morris水迷宫检测小鼠空间记忆学习能力、电镜观察海马及皮层神经元、突触的超微结构，应用免疫组化、Western blot和ELISA法检测不同干预组Aβ、Tau、分子伴侣蛋白系统、泛素-蛋白酶体系统和自吞噬-溶酶体系统的关键蛋白的差异。意义：揭示补肾化痰法中药治疗AD的可能生物效应靶点。

中文关键词： 阿尔茨海默病；金思维；补肾活血化痰法；蛋白质量控制；3×Tg-AD

英文摘要： Background: β-amyloid deposition and hyperphosphorylated tau are two core pathological changes in Alzheimer disease (AD), which have been found closely related with the dysregulation of protein quality control networks, thus the disruption of proteins' production, folding and degradation. Aim: GEPT, a Chinese herbal formula with activating blood and dissipating phlegm function, have been found effective in treating AD. Thus, present research aims at observing the influence of GEPT on behavioral, hippocampus and cortical pathological (ultra-structure of neurons and synapses, and β-amyloid and hyperphosphorylated tau depositions) changes in 3×Tg-AD transgenic mouse and then observing influence of GEPT on changes of chaperone, ubiquitin-proteasomal and autophagy- lysosomal systems in 3×Tg-AD mouse. Method: Diving platform experiment and Morris water maze experiment will be used to check memory and behavior of 3×Tg-AD transgenic mouse; electron microscope will be applied to observe ultra-structure of neurons; immunohistochemisty, Western blot and ELISA will be used to test expressions ofβ-amyloid tau and key proteins in chaperone system, ubiquitin proteasome system and autophagy-lysosome system. Application: The whole picture of protein quality control net in 3×Tg-AD transgenic mouse will be depicted and pharmaceutical targets in this networks of GEPT will be revealed.

英文关键词： Alzheimer's disease;GEPT;Reinforcing kidney activating blood and dissipitaing phlegm;Protein quality control;triple transgenic mouse