激活嗅觉通路的“嗅三针”调控阿尔茨海默病转基因模型小鼠Aβ-MAPK-MG的机制研究

项目名称： 激活嗅觉通路的“嗅三针”调控阿尔茨海默病转基因模型小鼠Aβ-MAPK-MG的机制研究

项目编号： No.81503667

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： 王渊

作者单位： 陕西中医药大学

项目金额： 18万元

中文摘要： 阿尔茨海默病（AD）是严重危害患者健康的老年性疾病，临床上我们应用嗅三针对其有较好疗效，但作用机制尚不明确。最新研究显示，本病与由β-淀粉样蛋白（Aβ）沉积促小胶质细胞(MG)活化启动和丝裂原活化蛋白激酶(MAPK)通路介导的炎症反应密切相关，而炎症反应能够直接导致神经元损伤，加速AD的发展。预实验中，我们观察到嗅三针能在嗅觉通路完整的情况下降低AD小鼠海马炎症因子水平和Aβ-MAPK表达，这可能是嗅三针的效应途径之一。因此，本研究拟将Aβ-MAPK-MG相联系，基于炎症反应这一相通环节，以切断和保留嗅觉通路的转基因AD小鼠为实验对象，采用分子生物学等技术，对“Aβ沉积-MAPK通路激活-MG活化-炎症因子释放”的链条效应进行系统研究，揭示嗅三针通过激活嗅觉通路发挥对Aβ-MAPK-MG的良性调控的作用机制，系统阐明嗅三针通过嗅觉通路治疗AD的分子机制，对本病的临床治疗具有理论和实际意义

中文关键词： 嗅三针；阿尔茨海默病；小胶质细胞；β-淀粉样蛋白；丝裂原活化蛋白激酶信号通路

英文摘要： Alzheimer's disease(AD) is a kind of senile disease which arouse severe harm to the health. We applied olfactory three needle therapy and have got good curative effect in clinic,but the mechanism is still not clear. The newest studies show that AD has close relationship with two aspects, firstly,β-amyloid protein(Aβ)deposition results in the activation of microglia(MG),then activated MG mediates inflammatory reaction,secondly,(mitogen-activated protein kinase)MAPK signal pathway mediates inflammatory reaction,and Inflammation can directly lead to neuronal damage, accelerates the development of AD .In preliminary study,we have observed that olfactory three needle therapy can reduced the level of inflammatory factor and Aβ-MAPK expression in hippocampus of AD mice under the integrity of olfactory pathway.This might be one of the effective pathways for olfactory three needle therapy. Consequently,we intend to establish the relationship among Aβ-MG-MAPK. Based on the same inflammatory response link, we will take AD transgenic mice as research object,with its’ olfactory pathway getting cut and kept, and apply molecular biology as test technique.We will undergo a systematic study on the chain effect of “Aβdeposition- the activation of MAPK pathway-MG activation- inflammatory factor release”.We initially reveal the mechanism of olfactory three needle therapy ,that is to say this therapy maybe benignly adjust the Aβ-MAPK-MG mutual regulation through activating olfactory pathway. At last,we systematically elucidate the molecular mechanism of olfactory three needle therapy in the treatment of AD through olfactory pathway，meanwhile,we expect to provide a theoretical and experimental basis for clinical treatment of AD with this therapy.

英文关键词： olfactory three needle ;Alzheimer’s disease;microglia;Aβ;MAPK signaling pathway