基于“通督启神”法探讨不同电针对AD模型小鼠不同脑区小胶质细胞活化通路的影响

Alzheimer's disease (AD) is defined as a dementing illness in which anterograde amnesia is a dominant symptom. With the increasing number of patients each year, the society burden is heavier. Our pervious study have found, the "dredging governor meridian and awakening mind" method have effects on curing AD by decreasing the generation of Aβ and promoting the clearance of Aβ. According to the latest research, the activation of microglia plays a key role in the pathogenesis of AD. However, it is unclear that whether the "dredging governor meridian and awakening mind" method take part in the regulation of microglia activity. On the basis of our last research of AD , we choose APP/PS1transgenic mice as the model of AD to study the effect of "dredging governor meridian and awakening mind" method on AD. Techniques including TSPO-micro PET, laser scanning confocal microscopy, immunoprecipitation ,immunohistochemistry and Western Blot will be applied to study the effects of different kinds of Electro-acupuncture(EA) on the activation of microglia. This study will aim at interpreting"dredging governor meridian and awakening mind" method in cell and molecular biology, and to explore the mechanism of different EA intervention on AD. Therefore to develop a new clinical treatment method for AD and provide its experimental basis.

阿尔兹海默病（AD）是以逐渐遗忘为主要特征的中枢神经系统退行性疾病，随着患病人数的逐年增高，社会负担愈加沉重。我们以往研究发现:"通督启神"针法可以通过减少Aβ的生成并促进其清除而有效治疗AD。最新研究显示:小胶质细胞的活化与聚集在AD的发病机制中发挥关键作用，而"通督启神"针法能否调节小胶质细胞的活化及其作用机制仍不清楚，因此，本课题选用转基因APP/PS1小鼠作为研究对象，从与AD发病密切相关的小胶质细胞活化途径入手，应用小胶质细胞TSPO正电子发射断层成像、激光扫描共聚焦、免疫共沉淀、免疫组化、Western blot等技术，从活体到病理组织等不同层面进行研究，通过检测并分析不同脑区小胶质细胞的活化状态及与其相关物质的变化，力求从分子生物学角度深入阐释"通督启神"法的理论内涵以及治疗AD的作用机制，为临床治疗AD开辟新的途径并提供科学实验依据。

本课题选用转基因APP/PS1小鼠作为研究对象，从与AD发病密切相关的小胶质细胞活化途径入手，应用PET成像、激光扫描共聚焦、免疫组化、Western blot等技术，从活体到病理组织等不同层面进行研究，通过检测并分析不同脑区小胶质细胞的活化状态及与其相关物质的变化，力求从分子生物学角度深入阐释“通督启神”法的理论内涵以及治疗AD的作用机制，为临床治疗AD开辟新的途径并提供科学实验依据。实验结果提示“通督启神”法脉冲电针干预能够有效改善AD模型小鼠的学习记忆能力及海马等有关脑区的能量代谢水平；同时提升小胶质细胞活化密切相关的免疫受体TREM2及有关蛋白DAP12、Syk、PI3K、Akt、PLC-γ的表达，抑制AD病理过程中小胶质细胞活化产物炎性因子TNF-α、IL-1β、IL-6、IL-12的释放。虽然脉冲电针、音乐电针、多奈哌齐及针药结合疗法在干预小胶质细胞活化方面各具优势，但在行为学改善方面，音乐电针结合药物疗法的优越性得以体现。