世界中医药2025，Vol.20Issue(10)：1661-1671,11.DOI:10.3969/j.issn.1673-7202.2025.10.004
基于网络药理学和动物实验研究复元益肾方治疗阿尔茨海默病机制
Mechanism of Fuyuan Yishen Formula in Treating Alzheimer's Disease Based on Network Pharmacology and Animal Experiments
摘要
Abstract
Objective:To investigate the therapeutic mechanism of Fuyuan Yishen Formula in the treatment of Alzheimer's disease(AD)based on network pharmacology combined with animal experiments.Methods:The Morris water maze test was used to evalu-ate the learning function of transgenic 5 × FAD mice carrying five gene mutations.Hematoxylin-eosin(HE)staining and immuno-histochemistry were employed to observe brain tissue pathology,and transmission electron microscopy(TEM)was used to examine neuronal ultrastructure.Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spec-trometry(LC-MS)was applied to characterize the chemical constituents of Fuyuan Yishen Formula.Common targets between the formula and AD were screened,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrich-ment analyses.Western blot(WB)was used to detect the expression of phosphorylated mammalian target of rapamycin(p-mTOR/mTOR),hypoxia-inducible factor-1α(HIF-1α),hexokinase 2(HK2),and tumor suppressor protein P53.Results:Compared with the model group,the Fuyuan Yishen Formula group significantly shortened the escape latency(P＜0.05),increased the number of platform crossings and the time spent in the target quadrant(P＜0.01),significantly downregulated β-amyloid(Aβ)expression in the hippocampus and cortex(P＜0.01),increased neuronal count,reduced Aβ plaque deposition,and improved the cytoplasmic morphology of neurons and microglia.LC-MS identified 145 chemical constituents in the formula,with 320 common targets related to AD.GO enrichment analysis yielded 2 832 biological processes,152 cellular components,and 293 molecular functions.KEGG a-nalysis revealed 198 signaling pathways,including the HIF-1α,P53,and mTOR pathways.WB results showed that protein expres-sion levels of p-mTOR/mTOR,HIF-1α,HK2,and P53 were significantly reduced in the Fuyuan Yishen Formula group compared to the model group.Conclusion:Fuyuan Yishen Formula exerts therapeutic effects on AD by reducing Aβ plaque deposition,impro-ving neuronal damage and microglial morphology,possibly through regulating the expression of p-mTOR/mTOR,HIF-1α,HK2,and P53 proteins.关键词
阿尔茨海默病/复元益肾方/网络药理学/小胶质细胞/低氧诱导因子-1α/抑癌基因53/哺乳动物雷帕霉素靶蛋白/己糖激酶2Key words
Alzheimer's disease/Fuyuan Yishen Formula/Network pharmacology/Microglia/HIF-1α/P53/mTOR/HK2分类
医药卫生引用本文复制引用
杜若飞,马慧芬,王自闯,贾亚泉,张振强,宋军营..基于网络药理学和动物实验研究复元益肾方治疗阿尔茨海默病机制[J].世界中医药,2025,20(10):1661-1671,11.基金项目
国家自然科学基金面上项目(82274612)——基于GLP-1R和PPAR-a介导的信号通路交互调节"自噬抗凋亡"探讨生慧汤干预阿尔茨海默病机制 （82274612）
河南省中医药科学院研究专项课题项目(2024Y1031)——复元益肾颗粒调节小胶质细胞糖代谢重编程抗AD药效物质基础及机制研究 （2024Y1031）
河南中医药大学科研苗圃工程项目(MP2023-08)——基于PI3K/Akt信号通路探讨胰岛素抵抗对AD的影响及六味地黄丸的干预作用 （MP2023-08）
