目的 探寻年龄相关性黄斑变性（age-related macular degeneration，AMD）能量代谢的关键基因和潜在调控的中药化合物。方法 从GEO数据库获取AMD相关Bulk RNA测序数据集GSE135092，利用R语言筛选差异表达基因，并与GSEA数据库下载的能量代谢相关基因（energy metabolism-related genes，EMRGs）映射取交集，获取AMD差异表达EMRGs，通过Cytoscape软件构建蛋白质相互作用（protein-protein interaction，PPI）、转录因子（transcription factor，TF）、微小RNA（microRNA，miRNA）网络。使用LASSO回归在差异表达EMRGs中筛选AMD标志物，构建风险评分。同时，将AMD相关Single-cell RNA测序数据集GSE188280进行主成分分析（principal component analysis，PCA）及统一流形逼近与投影（uniform manifold approximation and projection，UMAP）分析以聚 类降维，并进行细胞类型注释，进一步评估AMD关键差异表达EMRGs在不同细胞类型间的表达水平。将关键差异表达EMRGs导入Coremine Medical数据库中进行相关中药活性成分预测及分子对接、分子动力学验证。结果 筛选出6个AMD关键差异表达EMRGs：FOXO3、GSK3B、MEF2A、NCOA1、HDAC1、PPARG，并构建相应PPI、TF-mRNA、mRNA-miRNA网络。LASSO回归得出NCOA1、MEF2A、FOXO3、GSK3B表达与AMD发生呈正相关，HDAC1表达与AMD发生呈负相关。分析AMD相关Single-cell RNA测序将32 714个细胞分类为19个簇，使用marker基因将细胞簇鉴定为9种细胞类型，进一步得到HDAC1、MEF2A、FOXO3及NCOA1在内皮细胞中高表达。根据关键基因HDAC1、MEF2A、FOXO3筛选到9味中药及其285种活性成分，经分子对接及分子动力学模拟，其中丹参醇B治疗AMD潜力最大。结论 HDAC1和丹参醇B为AMD能量代谢的潜在关键基因及作用化合物。

Objective To explore the key energy metabolism-related genes (EMRGs) in age-related macular degeneration (AMD) and the potential regulated traditional Chinese medicine compounds. Methods The AMD related Bulk RNA sequencing dataset GSE135092 was obtained from GEO, and the differentially expressed genes (DEGs) were screened by R software. Next, the intersection of DEGs with EMRGs downloaded from the GSEA was conducted to obtain AMD differentially expressed EMRGs, and protein-protein interaction (PPI), transcription factor (TF), and microRNA (miRNA) network were constructed using Cytoscape software. Then, LASSO regression was performed to screen AMD markers in differentially expressed EMRGs and construct a risk score. Meanwhile, the AMD related single-cell RNA sequencing dataset GSE188280 was used to conduct principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis for dimensionality reduction and cluster, and making cell type annotation, and further evaluating the expression levels of key differentially expressed EMRGs in AMD among different cell types. Finally, key differentially expressed EMRGs were imported into the Coremine Medical database for prediction of relevant traditional Chinese medicine active ingredients, molecular docking and molecular dynamics verification. Results A total of six key differentially expressed EMRGs were screened in AMD: FOXO3, GSK3B, MEF2A, NCOA1, HDAC1 and PPARG. Corresponding PPI network, TF-mRNA and mRNA-miRNA regulatory networks were constructed. LASSO regression showed that the expression of NCOA1, MEF2A, FOXO3, and GSK3B was positively correlated with AMD, while the expression of HDAC1 was negatively correlated with AMD. A total of 32 714 cells from AMD related single-cell RNA sequencing analysis were classified into 19 clusters, and the cell clusters were identified as nine cell types using marker genes. Furthermore, it was found that HDAC1, MEF2A, FOXO3 and NCOA1 were highly expressed in endohelial cells. Finally, a total of 285 active ingredients from nine traditional Chinese medicines were screened through key genes HDAC1, MEF2A and FOXO3. After molecular docking and molecular dynamics simulation, danshenol B was the most potential therapeutic compound in the treatment of AMD. Conclusion HDAC1 and danshenol B are potential key energy metabolism-related gene and compound in AMD.

中国中医科学院科技创新项目（CI2021A02611）；北京市石景山区名医传承工作室师承项目（石卫健中医发[2020]6号）；国家自然科学基金项目（8187150711）；国家中医临床研究基地业务建设科研专项课题项目（JDZX2015285）；石河子大学2023年自主支持科研项目（ZZZC2023024）