益气活血法保护神经血管单元治疗阿尔茨海默病转基因小鼠的实验研究

项目名称： 益气活血法保护神经血管单元治疗阿尔茨海默病转基因小鼠的实验研究

项目编号： No.81503450

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 孙林娟

作者单位： 中国中医科学院西苑医院

项目金额： 18万元

中文摘要： 阿尔茨海默病（AD）占痴呆病人的80%以上。Aβ的沉积影响微血管，血管内皮生长因子（VEGF）、血管生成素（Ang）和成纤维生长因子（FGF）的合成、代谢障碍，使得神经血管单元（NVU）的功能障碍，胆碱能神经损害，影响RAGE/LRP-1系统，血脑屏障转运Aβ障碍，进一步加重Aβ沉积。VEGF维持NVU的正常功能具有重要作用。而最新的研究报道VEGF启动子多态性与AD没有相关性。首先，本课题旨在研究VEGF与AD的关系。单纯保护神经元的研究在动物试验中有效，人体无效。因此，从保护NVU的角度考虑AD的治疗更符合人体生理特点。本课题将应用APP/PS-1转基因小鼠，能够通过血脑屏障的塞络通胶囊进行干预，观察血管单位数量、VEGF、Ang、FGF、胆碱能神经受体、脑组织和脑脊液中Aβ的变化，观察疗效，研究中药通过保护NVU治疗AD，为中药通过多途径、多靶点治疗AD的研究提供新的理论基础及思路。

中文关键词： 阿尔茨海默病；神经血管单元；塞络通；血管内皮生长因子；益气活血法

英文摘要： Alzheimer's disease accounts for more than 80% of patients with dementia. Aβ deposits on the microvascular, which lead to the synthesis and metabolic disorders of vascular endothelial growth factor, angiopoietin and fibroblast growth factor . So it makes the neurovascular unit dysfunction, cholinergic nerve damage, the abnormal function of the receptor of advanced glycation end products / Low density lipoprotein receptor related protein -1(RAGE/LRP-1) system and the transporter Aβ barriers of blood brain barrier, that further exacerbate Aβ deposition. Vascular endothelial growth factor plays an important role in maintaining the normal function of neurovascular unit..But the latest research reported that there was no significant correlation of vascular endothelial growth factor promoter polymorphism and Alzheimer's disease. So, the study aim at researching the relationship between vascular endothelial growth factor and Alzheimer's disease. It is very effectively of some medicine in protecting the neuron in the animal experiment, but is invalid in human body. Therefore, it is more suitable to human physiological characteristics in the protection of neurovascular unit in Alzheimer's disease treatment. The APP/PS-1 transgenic mice will be treated with sailuotong capusule which can pass through the blood brain barrier. The effect of sailuotong will be observed in vascular unit number, vascular endothelial growth factor, angiopoietin, fibroblast growth factor, cholinergic receptor, the concentration changes of Aβ in brain tissue and cerebrospinal fluid. Traditional Chinese medicine can treat Alzheimer's disease through the protection of the neurovascular unit. It will provide novel theory and research ideas of traditional Chinese medicine in the treatment Alzheimer's disease basis on multi way, multi targets and multi effects.

英文关键词： Alzheimer's disease;Neurovascular unit;Sailuotong;Vascular endothelial growth factor;Supplementing qi and activating blood circulation