基于网络药理学研究补肾方治疗阿尔茨海默病的作用机制

目的：基于网络药理学方法分析补肾方治疗阿尔茨海默病的作用靶点及信号通路，阐明其可能的作用机制。方法：通过中药系统药理学数据库与分析平台（TCMSP）和中药分子机制生物信息学分析工具（BATMAN-TCM）检索补肾方的化学成分、作用靶点，运用Uniprot数据库查询靶点对应基因，利用GeneCards数据库收集阿尔茨海默病作用靶点，使用Venny 2.1将补肾方作用靶点与阿尔茨海默病作用靶点取交集，通过String平台构建蛋白质-蛋白质相互作用（PPI）网络。采用Metascape进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析。通过Cytoscape 3.7.1软件进行可视化分析。结果：从补肾方4味中药材中筛选获得45个化合物和相应靶点397个。将补肾方主要活性成分调控靶点与阿尔茨海默病的靶点取交集共获得48个关键靶点。共得到1 077生物过程（P<0.01），128条信号通路（P<0.01）。结论：补肾方作用于阿尔茨海默病核心靶点有AKT1、IL-6、CASP3、TNF、TP53。这些靶点共同参与IL-17信号通路、流体剪切应力与动脉硬化信号通路、HIF-1信号通路、血清素能突触通路、胰岛素抵抗通路发挥下调神经炎症反应、改善血管神经功能障碍、防止蛋白质错误折叠、影响神经递质、调节细胞代谢及线粒体功能等作用，并可以在疾病早期、通路上游进行干预，可能是补肾方治疗阿尔茨海默病的潜在机制。

Mechanism of Bushen Formula in Treating Alzheimer's Disease Based on Network Pharmacology

To predict the targets and signaling pathways of Bushen Formula so as to explore the possible mechanism of the formula in the treatment of Alzheimer''s disease(AD).Methods:The active components and targets of Bushen Formula were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM(BATMAN-TCM),and the genes corresponding to the targets were collected from Uniprot.The targets of AD were obtained from GeneCards.Venny 2.1 was used to identify the common targets shared by Bushen Formula and AD.A protein-protein interaction(PPI) network was established via String.Metascape was used to perform gene ontology(GO) annotation and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment.Cytoscape 3.7.1 was used to perform visual analysis.Results:Bushen Formula contained four herbs,which corresponded to 45 active components and 397 targets.Bushen Formula and AD shared 48 common targets,for which 1 077 GO terms(P<0.01) and 128 KEGG signaling pathways(P<0.01) were enriched.Conclusion:The key targets of Bushen Formula for treating AD include AKT serine/threonine kinase 1(AKT1),interleukin-6(IL-6),caspase 3(CASP3),tumor necrosis factor(TNF),and tumor protein p53(TP53).These targets participate cooperatively in multiple signaling pathways,such as IL-17 and hypoxia-inducible factor-1(HIF-1),fluid shear stress and atherosclerosis,serotonergic synapse,and insulin resistance signaling pathways,to down-regulate neuroinflammation,prevent protein misfolding,relieve vascular nerve dysfunction,affect neurotransmitters,and regulate cell metabolism and mitochondrial function.Moreover,they can intervene in the early stage of disease and upstream region of the pathways.