中文摘要
阿尔茨海默病(AD)是最常见的老年期痴呆,已成为全球公共健康所面临的重大挑战。目前尚缺乏有效的治疗措施。历代医家均认为肾精亏虚、髓海不足是本病的基本病机,补肾填髓法是基本治法。国内同行和课题组前期研究均提示补肾填髓法能通过抗炎、抗凋亡、抗氧化等多途径发挥治疗AD的作用,且预实验结果提示该治法能够通过调控海马相关蛋白BDNF、PSD-95、Shank1等多靶点起到治疗AD的作用。据此,我们推测补肾填髓法能通过多靶点、多途径发挥治疗AD的作用,但尚未见相关研究。因此,本项目拟以补肾填髓法为干预手段,选用快速老龄化模型小鼠作为研究对象,整合应用组织病理学、动物行为学、基于iTRAQ技术的定量蛋白组学、生物信息学、分子生物学等研究方法筛选补肾填髓法治疗AD的靶蛋白和阐明其整体作用机制。本研究结果将为补肾填髓法治疗AD提供更系统、更深入的科学实验依据,同时也为中医药治疗AD的研究提供新的思路和方法。
英文摘要
Alzheimer's disease (AD) is the most common form of dementia in the elderly, which is the major challenges facing the global public health. However, no effective strategies are available to against the disease today. Ancient and recent physicians acknowledged that the deficiency of kidney essence and brains is the key pathogenesis in the progression of the disease, and the Bushen Tiansui therapy is the essential treatment option for AD. In addition, the results of our previous research and that of other domestic researches also demonstrated that Bushen Tiansui therapy could treat AD by targeting multiple pathways of the AD pathogenesis, including neuroinflammation, apoptosis and oxidative stress. Moreover, the results of the preliminary experiment suggested that Bushen Tiansui therapy could treat AD by targeting associated protein in hippocampus, including BDNF, PSD-95, and Shank1. Therefore, we hypothesize that Bushen Tiansui therapy could treat AD via various targets and multiple pathways. However, the accurate targets and pathways of Bushen Tiansui therapy is not available. So, we used the Bushen Tiansui therapy as an intervention method, and senescence-accelerated prone mouse as AD model. The histopathology, behavioral experiments, iTRAQ-based quantitative proteomics technology, Bioinformatics, and cell biology technology were utilized to systematically reveal the target proteins of the Bushen Tiansui therapy, and to explore the whole mechanism of the Bushen Tiansui therapy. The results will provide more systematic and thorough evidences for the treating AD by Bushen Tiansui therapy, and provide new proofs and new ideas for the treatment of AD with traditional Chinese medicine.
