基于Ca2+-CaMKⅣ-CREB信号通路研究染料木素干预阿尔茨海默病机制

项目名称： 基于Ca2+-CaMKⅣ-CREB信号通路研究染料木素干预阿尔茨海默病机制

项目编号： No.81202941

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 蔡标

作者单位： 安徽中医药大学

项目金额： 23万元

中文摘要： 阿尔茨海默病(AD)已成为老年人主要死因之一。目前认为AD的发病与钙离子（Ca2+）-钙调蛋白依赖性蛋白激酶Ⅳ（CaMKⅣ）-环腺苷酸应答元件结合蛋白（CREB）信号通路失调密切相关。中医认为AD基本病机为髓减脑消、神机失调，以肾精亏虚为本，补肾精生脑髓为其治疗大法。大豆具有补肾益智作用，功能填精益髓，染料木素是大豆中所含异黄酮的主要活性成分。我们既往研究发现，大豆异黄酮及染料木素具有改善学习记忆功能、减少海马神经元丢失等从而发挥防治AD的作用。鉴此，本课题基于Ca2+-CaMKⅣ-CREB信号通路，拟采用体内外研究方法，运用激光共聚焦法、Western blot法、实时荧光定量PCR法、免疫组化等现代分子生物学实验技术手段，观察染料木素对AD模型Ca2+-CaMKⅣ-CREB信号通路关键物质的含量或表达的影响，探讨染料木素防治AD、改善学习记忆功能的作用机制，寻求临床防治AD的新方法。

中文关键词： 染料木素；阿尔茨海默病；神经保护；钙离子；信号通路

英文摘要： Alzheimer's disease (AD) has become one of the main causes of death of old people. Recently, the pathogenesis of AD is closely related to the disturbance of Ca2+-CaMKIV-CREB signal pathway. Traditional Chinese medical science considers the pathogenesis of AD as marrow depletion, brain deficit and mind malajustment and makes the kidney-jing deficiency as a principal part and nourishing kidney to produce marrow as an important way. Soybean can nourish kidney and benefit brain and nourish the bone marrow and genistein is the main active component of isoflavones contained in soybean. We previously found that soybean isoflavones and genistein could make anti-AD effects through improving study and memory ability and reducing the loss of hippocampal neurons.With in vivo and in vitro methods and modern molecular biology experimental techniques such as laser confocal technology, Western blot, Real-time PCR and Immunohistochemistry, the subject, based on Ca2+-CaMKIV-CREB signal pathway, investigates the effects of genistein on the contents or expressions of the key material of Ca2+-CaMKIV-CREB signal pathway in AD models, probes the mechanism of genistein intervening AD and improving study and memory ability and seeks a new method for clinical prevention and treatment of AD.

英文关键词： Genistein；Alzheimer's disease；neuroprotection；Ca2+；signal pathway