解毒通络法抑制AD血脑屏障转运Aβ的机制研究

项目名称： 解毒通络法抑制AD血脑屏障转运Aβ的机制研究

项目编号： No.81202686

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： 朱海燕

作者单位： 北京中医药大学

项目金额： 23万元

中文摘要： Aβ如何在大脑聚集增多是AD研究中的关键环节。新近的研究提示AD患者脑中可溶性Aβ可能主要来源于血液，而BBB是血循环物质进入大脑的主要屏障，其结构及功能的损害可直接导致有毒物质进入大脑，对神经元造成损伤。因此，研究AD病理状态下BBB对Aβ转运的改变将有助于从另一角度揭示AD的发病机制及作用靶点。本课题采用转基因老化痴呆小鼠模型和体外BBB模型，通过分子生物、免疫组化、放射免疫、透射电镜等技术手段，分别从体内和体外观察BBB对Aβ的细胞内转运途径和细胞旁转运途径的变化，并深入探讨经RAGE-Aβ触发ROS - - ERK1/2/PKC - - NF-κB 信号通路激活与Aβ相关转运蛋白表达之间的相互复杂关系。同时，基于"毒损脑络"的中医病机假说，以清开灵进行干预，为"解毒通络"治法的扩展应用提供初步的实验依据.

中文关键词： β-淀粉样蛋白；阿尔茨海默病；血脑屏障；清开灵注射液；

英文摘要： How the Aβ was aggregated in the brain is the point in study on Alzheimer's disease. Recent studies have suggested that soluble Aβ in brain of AD patients may mainly comes from the blood, and BBB is the barrier of brain that inhibiting substances from the blood into the brain. The damage of structure and function of BBB could lead to neuronal injury caused by toxic substances from blood. Therefore, research on BBB in AD will be helpful to reveal the pathogenesis of AD and target from another angle. The study adopt the animal model of transgenic mice with dementia model and BBB in vitro model, to observe the changes of Aβ transported on BBB by the means of molecular biology, immunochemistry, radioimmunoassay, transmission electron microscopy and other technical means. Furthermore, the complex interaction of relationships of ROS-ERK1/2/PKC-NF-κB signaling pathway triggered by RAGE and Aβ transporter protein will be explored. At the same time, based on the TCM pathogenesis hypothesis of " the injury of collaterals by toxins", with Qingkailing intervention, to provide preliminary experimental evidence for the extended application of " dispelling toxins and dredging collaterals " treatment.

英文关键词： β-amyloid；Alzheimer's disease；blood brain barrier；Qingkailing Injection；