MEOX2基因调控的血管性因素与阿尔兹海默病病理机制的相关性研究

项目名称： MEOX2基因调控的血管性因素与阿尔兹海默病病理机制的相关性研究

项目编号： No.81202540

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 旷喜

作者单位： 四川大学

项目金额： 23万元

中文摘要： 阿尔兹海默病（AD）是一种以进行性认知功能障碍和行为损害为特征的脑退行性疾病。目前对AD病因和发病机制的研究仍未完全清楚，临床上极度缺乏预防治疗AD的有效药物。传统观点认为AD是老年变性病，脑内淀粉肽Aβ沉积是AD病理的始发因素和核心，病因与遗传、病毒感染、炎症、胆碱系统功能障碍等因素相关。近年来对AD发病机制的研究发现AD病理过程中的血管性因素与认知功能的衰退关系密切。目前已有的研究提示血管性损伤不仅在AD疾病中存在甚至在发病过程中更早于传统意义上的AD病理损伤。同源盒MEOX2基因又称为GAX基因，主要在心血管系统中高表达，对血管的分化起多方面作用。目前国内外未见从血管性因素角度探讨MEOX2基因在AD疾病发展不同阶段中作用的研究。本课题拟从AD疾病发展过程中微血管系统损伤重建的角度，研究MEOX2基因调控的血管性因素在疾病病理发展过程中的作用及其机制，为AD疾病的治疗寻找新的思路。

中文关键词： MEOX2；阿尔兹海默病；血脑屏障；淀粉肽；血管内皮功能

英文摘要： Alzherimer's disease (AD) is an age-related neurodegenerative disease which is characterized clinically by progressive loss of memory and cognitive funcitons. Current theapeutic strategies have failed to provide an effective cure or prevention for AD. AD is a complex and multifactorial neurological disorders, the pathogenesis of AD still remains unclear. Traditional view thought the core and intial pathogenesis of AD were progressive accumulation of various aggregates of β-amyloid(Aβ) peptides oligomers in brain, associated with genetic risk factors, virus infection, inflammation and cholinergic system dysfunciton. Recently, there is evidence from epidemiological, pathological and clinical reports suggest that vascular disorders in brain of individuals with AD contributes to the extremes of this diesase. This hypothesis states that primary damage to brain microcirculation initiates a non-amyloidogenic pathway of vascular-mediated neuronal dysfunciton and injury, which is mediated by BBB dysfunction and is associated with leakage and secretion of multiple neurotoxic molecules and diminished brain capillary flow that causes multiple focal ischaemic or hypoxic microinjuries. Cerebral hypoperfusion has been shown to be a preclinical condition and a most accurate indicator for prediction whether people will develop

英文关键词： MEOX2；Alzheimer's disease；blood brain barrier；amyloid beta；vascular endothelial funtion