世界中医药

目的:通过网络药理学和分子对接方法探讨中药“黄芪-当归”治疗年龄相关性黄斑变性(AMD)的作用机制。方法:借助中药系统药理学数据库与分析平台（TCMSP）获取中药黄芪、当归的有效成分与作用靶点,使用Uniport数据库进行基因ID的注释,在GeneCards、OMIM数据库中查找AMD的相关基因。使用Cytoscape 3.7.2将药物-关键有效成分-疾病靶点网络可视化,在String数据库平台构建蛋白质-蛋白质相互作用(PPI)网络,再利用Metascape基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析,使用AutoDock4.2.6软件对关键靶点蛋白及有效成分进行分子对接验证。结果:通过筛选,得到黄芪-当归有效成分22个,与AMD相关的关键有效成分14个,黄芪-当归与AMD的共同基因靶点52个;PPI中核心基因依次为CASP3、IL6、VEGFA、EGFR、ESR1等;GO功能富集得到1 064个条目,生物学过程主要涉及细胞凋亡、对类固醇激素的反应、活性氧代谢、对脂多糖的反应等;KEGG富集分析后得到119条信号通路,与癌症的通路、流体剪切力与动脉粥样硬化、HIF-1信号通路、TNF信号通路、VEGF信号通路等机制相关;分子对接结果表明,核心有效成分可与靶点蛋白形成构象能量较低、结构稳定的对接。结论:“黄芪-当归”治疗AMD具有多成分、多靶点、多通路的特点,为进一步研究AMD的治疗提供了思路。

English Summary:

To explore the mechanism of Astragali Radix and Angelicae Sinensis Radix in the treatment of age-related macular degeneration(AMD) based on network pharmacology and molecular docking.Methods:The active ingredients and targets of Astragali Radix and Angelicae Sinensis Radix were obtained from TCMSP，and Uniport was used to annotate gene IDs.AMD-related genes were screened out in GeneCards and OMIM.Cytoscape 3.7.2 was used to visualize the drug-key active ingredient-disease target network and protein-protein interaction(PPI) network was plotted by String.Metascape was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses.AutoDock 4.2.6 was used for molecular docking of key target proteins to active ingredients.Results:Twenty-two ingredients of Astragali Radix and Angelicae Sinensis Radix were screened out，14 of which were key active ingredients related to AMD.There were 52 common gene targets of drugs and the disease.The core genes in the PPI network were CASP3，IL6，VEGFA，EGFR，ESR1，etc.GO function enrichment resulted in 1 064 entries，with biological processes mainly involving apoptosis，response to steroid hormones，active oxygen metabolism，and response to lipopolysaccharide.KEGG enrichment yielded 119 signaling pathways，which were related to cancer pathway，fluid shear force and atherosclerosis，HIF-1 signaling pathway，TNF signaling pathway，and VEGF signaling pathway.Molecular docking results showed that the core active ingredients could dock to the target proteins with low conformational energy and stable structure.Conclusion:The therapeutic effect of Astragali Radix and Angelicae Sinensis Radix on AMD is characterized by multiple components，multiple targets，and multiple pathways.This study is expected to provide a scientific basis for further research on the treatment of AMD.

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