摘 要：运用网络药理学和海马代谢组学技术研究开心散治疗阿尔茨海默病（AD）的潜在药物成分和作用机制。采用APP/PS1雄性小鼠作为AD模型，Morris水迷宫实验观察小鼠学习记忆能力，苏木精-伊红（HE）染色法观察小鼠海马CA1区病理变化。通过网络药理学对开心散入海马成分靶点和疾病靶点取交集，进行GO分析和KEGG通路富集分析，并进行蛋白质-蛋白质互作网络和分子对接分析。采用液相色谱-串联质谱（LC-MS/MS）代谢组学技术对小鼠海马进行代谢物检测，并筛选差异代谢物和代谢通路富集分析，最终将网络药理学和代谢组学结果进行综合分析。Morris水迷宫实验表明，开心散可以改善APP/PS1小鼠学习记忆能力；HE染色结果表明，开心散对小鼠中枢神经损伤有改善作用。LC-MS/MS鉴定出开心散入海马化合物466个，潜在治疗靶点87个，KEGG富集通路主要有脂质与动脉粥样硬化、胞葬作用、AD等；分子对接结果表明，开心散潜在药效成分和关键靶点结合水平较高。从海马中共筛选出501个差异代谢物，富集出6条代谢通路，通过网络药理学与代谢组学通路进行交集分析，得到亚油酸代谢和胆碱能突触等代谢通路。本研究表明，开心散入海马成分能够靶向AD疾病靶点，这些靶点与亚油酸代谢和胆碱能突触等通路相关，这可能是开心散治疗AD的潜在作用机制。

关键词：阿尔茨海默病；开心散；网络药理学；代谢组学；分子对接
中图分类号：R287；R242       文献标志码：A                  DOI：10.3969/j.issn.1007-7146.2025.05.006

Abstract: This study combined network pharmacology and hippocampal metabolomics to explore the active components and mechanism of kaixinsan (KXS) in treating Alzheimer’s disease (AD). APP/PS1 male mice were used as the AD model. The morris water maze test was performed to evaluate learning and memory abilities, and hematoxylin-eosin (HE) staining was conducted to observe pathological changes in the hippocampal CA1 region. Through network pharmacology, common targets between KXS components in hippocampus and AD-related targets were identified, followed by gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) network construction and molecular docking. Hippocampal metabolites were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and differential metabolites were screened for metabolic pathway enrichment analysis. Finally, comprehensive analysis was performed by integrating network pharmacology and metabolomics results. The morris water maze test shows that KXS improves learning and memory abilities in APP/PS1 mice. HE staining results indicate that KXS ameliorates central nervous system damage. LC-MS/MS identifies 466 KXS-derived compounds in hippocampus and 87 potential therapeutic targets. The main KEGG enriched pathways include lipid and atherosclerosis, efferocytosis, and AD pathways. Molecular docking results demonstrate high binding affinity between KXS potential active components and key targets. A total of 501 differential metabolites are screened from hippocampus, enriching 6 metabolic pathways. Integrated analysis of network pharmacology and metabolomics pathways yields intersecting pathways including linoleic acid metabolism and cholinergic synapse. This study reveals that KXS components in hippocampus can target AD-related disease targets, which are associated with pathways such as linoleic acid metabolism and cholinergic synapse. These findings may explain the potential mechanism of KXS in treating AD.
Key words: Alzheimer’s disease; kaixinsan; network pharmacology; metabolomics; molecular docking
（Acta Laser Biology Sinica, 2025, 34(5): 426-441）