标题：基于网络药理学的多奈哌齐联合丁苯酞治疗阿尔茨海默病的机制研究

      作者：王慧娟 1，2，叶端玲 1，许云腾 3，许文勇 1    王慧娟 1，2，叶端玲 1，许云腾 3，许文勇 11.福建中医药大学附属厦门第三医院神经内科，福建 厦门 361100；2.福建中医药大学中西医结合学院，福建 福州 350122；3.福建中医药大学中西医结合研究院，福建 福州 350122

      卷次： 2024年35卷4期

      【摘要】 目的 研究多奈哌齐联合丁苯酞治疗阿尔茨海默病(AD)的疗效与潜在作用机制。方法 采用网络药理学方法，利用疾病及药物数据库中获取AD和丁苯酞、多奈哌齐的作用靶点，将其导入到 STRING11.0数据库中，得到潜在作用靶点的PPI网络图，并结合Cytoscape3.8.1软件和 cytoHubba插件筛选排名前 10的核心基因，进行GO功能富集分析和KEGG通路富集分析，以深入研究多奈哌齐联合丁苯酞在治疗AD中的潜在作用机制。结果 共获得联合药物靶点 249个；1 236个疾病基因靶点，获得 77个药物-疾病交集靶点，排名前 10的Hub基因为 IL1B、PTGS2、STAT3、EGFR、MMP9、CCL2、IGF1、GSK3B、JAK2、ICAM1。GO富集和KEGG富集分析发现，这些靶点主通过抗炎、抗氧化应激、调节受体活性，改善神经信号传递、调节酶活性、保护血脑屏障、逆转突触可塑性、抑制神经细胞凋亡等多种途径来达到协同多奈哌齐有效治疗AD。结论 多奈哌齐联合丁苯酞有效治疗AD的主要机制包括协同作用以及通过更多作用靶点和信号通路来实现抗炎、抗氧化应激、改善血管储备功能、抑制细胞凋亡等多重机制。
      【关键词】 阿尔茨海默病；丁苯酞；多奈哌齐；网络药理学；药物靶点；疾病基因靶点；潜在作用机制
      【中图分类号】 R742 【文献标识码】 A 【文章编号】 1003—6350（2024）04—0564—06

Mechanism study of donepezil combined with butylphthalide in the treatment of Alzheimer's disease based onnetwork pharmacology.
WANG Hui-juan 1,2, YE Duan-ling 1, XU Yun-teng 3, XU Wen-yong 1. 1. Department ofNeurology, Xiamen Third Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Xiamen 361100, Fujian,CHINA; 2. College of Integrated Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou350122, Fujian, CHINA; 3. Institute of Integrated Chinese and Western Medicine, Fujian University of Traditional ChineseMedicine, Fuzhou 350122, Fujian, CHINA
【Abstract】 Objective To investigate the efficacy and potential mechanism of donepezil combined with bu-tylphthalide in the treatment of Alzheimer's disease (AD) using network pharmacology.Methods In this study, we usednetwork pharmacology to analyze the therapeutic effect of donepezil combined with butylphthalide in the treatment ofAD. The targets of donepezil and butylphthalide were obtained from the database of diseases and drugs, and the potentialtargets were further analyzed by bioinformatics methods. STRING11.0 database was used to generate a protein-proteininteraction (PPI) network of potential targets, and Cytoscape3.8.1 software and cytoHubba plugin were used to screenthe top 10 core genes. Gene ontology (GO) function and KEGG pathway enrichment analysis were performed to furtherexplore the potential mechanism of donepezil combined with butylphthalide in the treatment of AD. Results A total of249 drug targets and 1 236 disease gene targets were obtained, and 77 drug-disease intersecting targets were identified.The top 10 hub genes were IL1B, PTGS2, STAT3, EGFR, MMP9, CCL2, IGF1, GSK3B, JAK2, and ICAM1. GO func-tion and KEGG pathway enrichment analysis showed that these targets mainly act through multiple mechanisms such asanti-inflammatory effect, antioxidant stress, regulation of receptor activity, improvement of neural signal transduction,regulation of enzyme activity, protection of blood-brain barrier, reversal of synaptic plasticity, and inhibition of neuronalapoptosis to achieve effective treatment of AD. Conclusion The main mechanisms of donepezil combined with bu-tylphthalide in the treatment of AD include synergistic effects and multiple mechanisms such as anti-inflammatory ef-fect, antioxidant stress, improvement of vascular reserve function, and inhibition of cell apoptosis through more targetsand signaling pathways.
      【Key words】 Alzheimer's disease; Butylphthalide; Donepezil; Network pharmacology; Drug targets; Diseasegene targets; Potential mechanism