目的 运用网络药理学结合加权基因共表达网络分析（WGCNA）探究黄精治疗代谢性相关脂肪性肝病的作用机制。方法 利用中药系统药理数据分析平台（TCMSP）检索黄精主要活性成分，并采用Pharm Mapper平台挖掘黄精活性成分相关靶点。在GeneCards数据库中下载并整理了代谢性相关脂肪性肝病相关基因。通过GEO平台下载代谢性相关脂肪性肝病相关基因芯片GSE89632，使用R软件limma包进行差异分析，并运用WGCNA筛选出的模块基因作为疾病靶点基因。R软件Venn Diagram包进行交集分析并可视化。采用R软件clusterProfiler包对交集靶点基因进行基因本体论（GO）功能富集和京都基因与基因组百科全书（KEGG）信号通路富集分析。采用Cytoscape软件进行“药物–活性成分–共同靶点”网络的构建与分析。将交集靶点基因上传至String数据库，把结果数据导入至Cytoscape软件构建蛋白相互作用（PPI）网络并筛选核心靶点基因。采用MOE软件进行分子对接。结果 共筛选出黄精活性成分12个，成分相关靶点327个；GeneCards数据库整理获得代谢性相关脂肪性肝病相关基因1 227个；WGCNA关联模块基因2 639个；最终获得黄精治疗代谢性相关脂肪性肝病靶点基因18个。富集分析发现18个靶点基因通过调控胰岛素抵抗、脂质和动脉粥样硬化、代谢性相关脂肪性肝病等信号通络，参与细胞间信号传导、脂质代谢、氧化应激、炎症反应等生物过程。分子对接研究显示核心靶点与相关黄精活性成分结合稳定。结论 黄精具有治疗代谢性相关脂肪性肝病的作用，且在治疗代谢性相关脂肪性肝病中具有多靶点、多成分、协同作用的特点。

Objective To investigate the mechanism of Polygonati Rhizoma in treatment of metabolically associated fatty liver disease by network pharmacology and WGCNA. Methods The TCMSP database was used to retrieve the main active ingredients of Polygonati Rhizoma and the active ingredient-related targets were predicted by PharmMapper. The genes related to metabolically associated fatty liver disease were obtained from GeneCards, and the gene chip data (GSE89632) related to metabolically associated fatty liver disease was downloaded from the GEO platform, and the limma package of R software was used for differential analysis, and the module genes selected by WGCNA were used as disease target genes. R software Venn Diagram package for intersection analysis visualization. R software clusterProfiler package was used to perform gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis for intersection target genes. Cytoscape software was used to construct and analyze the "active ingredient-common target" network. The intersection target genes were uploaded to String database, and the result data were imported into Cytoscape software to construct protein interaction network (PPI) and screen the core target genes. Molecule operating environment (MOE) software was used to verify the molecular docking between active components and core targets. Results A total of 12 active ingredients and 327 related targets were screened out. A total of 1 227 genes related to metabolically associated fatty liver disease were obtained from GeneCards database. 2 639 WGCNA associated module genes. Finally, 18 target genes were obtained for the treatment of metabolically associated fatty liver disease with Polygonati Rhizoma. Enrichment analysis showed that 18 target genes were involved in cellular signaling, lipid metabolism, oxidative stress, inflammation and other biological processes by regulating insulin resistance, lipid and atherosclerosis, and metabolically associated fatty liver disease. Molecular docking studies showed that the core target was stable in binding with related active components. Conclusion Polygonati Rhizoma has an effect of treating metabolically associated fatty liver disease, and which showed the characteristics of multi-target, multi-component, and synergistic effects on the treatment of metabolically associated fatty liver disease.

R285；R975

国家自然科学基金资助项目（82100488）；陕西省重点研发计划项目（2021SF-071）；陕西省教育厅科学研究项目（21JS012）；国家级大学生创新创业训练计划项目（202210716019）