目的 通过网络药理学和分子对接技术探究黄芪治疗原发性肾病综合征的作用机制。方法 综合运用TCMSP、HERB、BATMAN、ETCM数据库筛选黄芪的活性成分及靶点。通过OMIM、TTD、GeneCards数据库筛选原发性肾病综合征靶点，利用Venny工具获取交集靶点。采用Cytoscape 3.10.0软件构建“药物–活性成分–靶点–疾病”网络并分析，基于STRING数据库构建蛋白质相互作用（PPI）网络，通过Metascape数据库进行京都基因与基因组百科全书（KEGG）富集分析及基因本体（GO）富集分析。利用分子对接技术验证核心成分与靶点的结合亲和力。结果 筛选出黄芪17种活性成分及209个潜在靶点，与原发性肾病综合征的4 302个靶点比对后，确定128个共同靶点。“药物–活性成分–靶点–疾病”网络显示常春藤皂苷元、华良姜素、山柰酚等为核心成分，核心靶点为肿瘤蛋白p53（TP53）、Jun原癌基因（JUN）、蛋白激酶B1（Akt1）等；GO分析显示交集靶点主要参与对脂多糖的响应、凋亡信号通路调控等生物学过程，涉及膜筏、蛋白激酶复合体等细胞组分及类泛素蛋白连接酶结合等分子功能；KEGG分析主要富集于白细胞介素-17（IL-17）信号通路等。分子对接结果显示，核心活性成分常春藤皂苷元、华良姜素、山柰酚与核心靶点TP53、JUN、Akt1均具有良好结合亲和力，其中常春藤皂苷元与Akt1结合亲和力最低。结论 黄芪通过常春藤皂苷元等核心活性成分，作用于Akt1等核心靶点，调控IL-17等信号通路发挥治疗原发性肾病综合征的作用。

Objective To investigate the mechanism of Astragali Radix in treating primary nephrotic syndrome through network pharmacology and molecular docking techniques. Methods The active components and targets of Astragali Radix were screened using multiple databases including TCMSP, HERB, BATMAN, and ETCM. Primary nephrotic syndrome-related targets were identified from OMIM, TTD, and GeneCards databases, and the intersecting targets were obtained using the Venny tool. Cytoscape 3.10.0 software was used to construct and analyze the “drug-active ingredient-target-disease” network. PPI network was constructed based on the STRING database. KEGG pathway enrichment analysis and GO enrichment analysis were performed using the Metascape database. Molecular docking technology was used to validate the binding affinity between core components and targets. Results A totol of 17 active components and 209 potential targets of Astragali Radix were screened. After comparison with 4 302 primary nephrotic syndrome-related targets, 128 common targets were identified. The “drug-active ingredient-target-disease” network revealed that, hederagenin, kumatakenin, kaempferol, were the core components, and the core targets were TP53, JUN, Akt. GO analysis revealed that the intersection targets were mainly involved in biological processes such as responses to lipopolysaccharides and regulation of apoptotic signaling pathways, and were involved in cellular components such as membrane rafts and protein kinase complexes, as well as molecular functions such as ubiquitin-like protein ligase binding. KEGG analysis is mainly enriched in the IL-17 signaling pathway, etc. The molecular docking results showed that the core active ingredients, such as hederagenin, kumatakenin, kaempferol, all had good binding affinities with the core targets TP53, JUN, and Akt1, among which hederagenin had the lowest binding affinity with Akt1. Conclusion Astragali Radix exerts therapeutic effects on primary nephrotic syndrome by acting on core targets such as Akt1 and regulating signaling pathways like IL-17 through its core active components like hederagenin.

R287.3

黑龙江省中医药科研项目（ZHY2020-039）