我们前期研究表明：天麻素具有抗炎和神经保护作用。但缺乏系统的研究天麻素在阿尔茨海默氏病病理过程中抑制小胶质细胞激活，减轻神经炎症的保护作用及信号转导机制。课题拟通过Aβ前体蛋白过表达阿尔茨海默病转基因小鼠与D-半乳糖腹腔注射加侧脑室一次性注射聚集态的Aβ1－42 构建人工复合型阿尔茨海默氏病大鼠、原代培养小胶质细胞和BV-2小胶质细胞株等阿尔茨海默病氏动物与细胞模型，研究（1）天麻素在调控小胶质细胞激活中的作用；（2）天麻素对小胶质细胞激活相关关键信号通路：WNT / β-catenin与 Notch 信号、有丝分裂原活化蛋白激酶(MAPKs)信号与核因子-κB信号、肿瘤抑制基因激酶 LKB1 / AMP 活化蛋白激酶/Sir2 哺乳动物同源物信号通路的调控作用。从分子、细胞及整体层面探讨天麻素在抑制小胶质细胞激活，对抗阿尔茨海默氏病病理发生过程中的作用及其信号转导机制。

We have previously demonstrated that gastrodin plays potential anti-inflammatory and neuroprotective role in Alzheimer's disease. but its role and signal transduction mechanisms on inhibitory effects of microglial activation in anti-pathogenesis of Alzheimer's disease are not well known. By using amyloid precursor protein-transgenic mice and the Alzheimer's disease rat models which were established by intra-peritoneal injection of D-galactose combined with Aβ1-42 injection into bilateral lateral cerebral ventricle, primary microglial cells and murine BV-2 microglial cells, we arrange to investigate: (1) The therapeutic role of gastrodin on inhibitory effects of microglial activation in anti-pathogenesis of Alzheimer's disease; (2) Effects of gastrodin on signal transduction pathways which play a crucial role in determinating the microglial activation in anti-pathogenesis of Alzheimer's disease such as WNT / β-catenin signal and Notch signal pathway, mitogen-activated protein kinases (MAPKs) signal transduction and nuclear factor-κB (NF-κB) signal pathway and the tumor suppressor kinase LKB1 / AMP-activated protein kinase (AMPK)/ a mammalian ortholog of Sir2 (SIRT1) signal pathway. Taking together, the research arrange to study the role and signal transduction pathway of gastrodin in pathogenesis of Alzheimer's disease at molecular, cellular and individual levels in order to provide new evidences for inhibitory effects of microglial activation and treatment of Alzheimer's disease.