益肾化浊法调控炎性衰老过程防治阿尔茨海默病记忆减退的机制研究

阿尔茨海默病（AD）是与衰老相关的退行性疾病，预防和早期治疗意义重大。炎性衰老过程在AD发生、发展中扮演重要角色，小胶质细胞（MG）是其调控核心。MG既能释放过量炎症因子诱发AD，亦能吞噬病理产物减轻炎症反应延缓AD进展，该功能受TREM2/TLR4/NF-κB通路调节。前期研究发现益肾化浊法组方（YHD）可改善AD患者记忆减退，增加SAMP8鼠海马TREM2表达，减轻炎症反应，但具体机制不明。本项目结合中医治未病理论，从未病先防和既病防变层面，着眼于AD发病前和早期，以改善MG功能调节炎性衰老过程为切入点，拟用3和6月龄SAMP8鼠与BV2细胞为研究对象，结合RNAi技术，采用行为药理学、细胞和分子生物学方法观察YHD调控TREM2/TLR4/NF-κB通路中关键靶点表达，减轻神经炎症，进而预防并延缓AD记忆减退的作用机制，为部分阐释该方防治AD中治未病理论的现代生物学基础提供实验依据。

Alzheimer's disease (AD) is an age-related degenerative disease, and the prevention and early treatment are very important. The inflamm-aging process plays an important role in the onset and development of AD, and microglia (MG) is the core role in its regulation. MG can not only release excessive inflammatory factors to induce AD, but also can swallow pathological products to reduce inflammation and delay the progression of AD, and the function is regulated by TREM2/TLR4/NF-κB pathway. Previous studies have found that Yishen Huazhuo Decoction (YHD) could improve memory loss in AD patients, increase the expression of TREM2 in the hippocampus of SAMP8 mice, and reduce inflammation, but the specific mechanism is still unknown. In this study, focusing on the pre-stage and early stages of AD, with the combination of the idea of “prevention before disease onset” and “preventing disease from exacerbating” of “preventive treatment of disease” theory in traditional Chinese medicine, we try to conduct the study of YHD improving the function of MG to regulate the inflamm-aging process. 3 and 6-month-old SAMP8 Mice and BV2 cells will be used in the study combined with RNAi technology. Behavioral pharmacology, cell and molecular biology methods will be applied to explore the mechanism of YHD preventing and delaying AD memory loss by regulating the expression of key targets in the TREM2/TLR4/NF-κB pathway to reduce neuroinflammatory response. The study may provide experimental basis for partially elucidating the modern biological basis of YHD preventing and treating AD.