二苯乙烯苷对APP转化和调控的影响及其作用机制

β淀粉样蛋白（Aβ）级联学说是目前老年性痴呆（AD）发病机制的主流学说。Aβ是各种原因诱导AD的共同通路。APP（β淀粉样前体蛋白）是Aβ的前体物质，研究药物对APP的早期干预比直接干预Aβ更有效。二苯乙烯苷（TSG）是常用中药何首乌的主要成分，前期研究证实TSG具有良好的抗痴呆作用，是一种具有很大开发潜力的神经保护新药，但TSG对AD关键物质APP的转化和调控的影响尚未见报导。本项目拟在前期研究基础上，以高表达人类APP的APP695V717I转基因鼠为模型，进一步观察TSG对AD发病关键物质APP的转化及其调控的分泌酶、分泌酶调控因子与其基因表达的影响，并通过表面增强激光解吸离子化飞行时间质谱（SELDI-TOF-MS）技术检测TSG对APP转基因鼠大脑皮层和海马区蛋白质差异表达的影响，阐明差异表达的蛋白质与分泌酶及其调控因子之间的关系，为开发AD早期干预药物及其机制提供实验依据。

The hypothesis of beta-amyloid protein (Aβ) cascade has been accepted as mainstream theory in early pathogenesis of Alzheimer's disease (AD). Aβ is a common pathway of AD induced by a variety of reasons. APP is the precursor of Aβ. Studies have shown that early intervention of APP is more effective than direct intervention of Aβ. Stilbene glucoside (TSG) is the main component of Polygonum multiflorum. Previous studies suggested that the anti-dementia effect of TSG and its potential for development as a neuroprotective agents. But the effect of TSG on transformation and regulation of APP in AD has not been reported. On the basis of preliminary studies, this project is designed to detect the effect of TSG on secretases, secretases regulating factor and its gene expression on the transformation and regulation of APP in APP695V717I transgenic mouse. The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) is used to detect the effect of TSG on protein differential expression in cerebral cortex and hippocampus of APP transgenic mouse. The relationship between differentially expressed proteins and secretases and their regulatory factors are investigated and try to provide the experimental basis for the development of drugs for AD.