目的 通过网络药理学和分子对接技术探讨肾炎四味片治疗慢性肾炎的活性成分和作用机制。方法 采用TCMSP、ETCM、GeneCards等数据库收集肾炎四味片的活性成分和靶点以及慢性肾炎靶点。随后，采用Cytoscape软件和STRING数据库分别绘制肾炎四味片治疗慢性肾炎成分–靶点网络图和交集靶点的蛋白质相互作用网络。运用欧易云平台对交集靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。此外，采用分子对接技术验证肾炎四味片治疗慢性肾炎的核心成分和主要靶点的结合强度。结果 肾炎四味片治疗慢性肾炎的活性成分有128种，槲皮素、芹菜素、汉黄芩素、山柰酚、黄芩素和毛蕊异黄酮等为治疗慢性肾炎的主要活性成分。筛选得到肾炎四味片治疗慢性肾炎的交集靶点有119个，主要有免疫炎症因子前列腺素内过氧化物合酶2（PTGS2）、核因子κ-B亚基1（NF-κB1）、肿瘤坏死因子（TNF）、花生四烯酸5-脂氧合酶（ALOX5）、白细胞介素-6（IL-6）、基质金属蛋白酶9（MMP9），生长因子表皮生长因子受体（EGFR）、血管内皮生长因子A（VEGFA）、血红素加氧酶1（HMOX1）、转化生长因子β1（TGFB1），凋亡因子半胱天冬蛋白酶-3（CASP3）、半胱天冬蛋白酶-8（CASP8）、B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（BAX），激酶类磷酸肌醇-3-激酶催化亚基α（PIK3CA）、蛋白激酶B1（Akt1）、有丝裂原激活蛋白激酶-1（MAPK1）。此外，肾炎四味片治疗慢性肾炎主要通过调控TNF、IL-17、HIF-1和PI3K/Akt信号通路。通过分子对接证实肾炎四味片的活性成分与慢性肾炎靶点有较好的对接活性。结论 肾炎四味片的活性成分可能通过调控炎症、生长和凋亡相关的靶点和通路发挥治疗慢性肾炎的作用。

Objective To explore the active components and mechanism of Shenyan Siwei Tablets in treatment of chronic nephritis based on network pharmacology and molecular docking technology. Methods TCMSP, ETCM, GeneCards and other databases were used to collect the active components and targets of Shenyan Siwei Tablets and targets of chronic nephritis. Subsequently, Cytoscape software and STRING database were used to draw the network diagram of active components and intersection targets of Shenyan Siwei Tablets in the treatment of chronic nephritis, and the protein interaction diagram of intersection targets. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out on the intersection targets by using the Ouyi Cloud platform. In addition, molecular docking technology was used to verify the binding strength of the core components and targets of Shenyan Siwei tablets in the treatment of chronic nephritis. Results There are 128 active ingredients of Shenyan Siwei Tablets in the treatment of chronic nephritis, and quercetin, apigenin, wogonin, kaempferol, baicalin and calycosin were the main active ingredients in treatment of chronic nephritis. A total of 119 intersection targets of Shenyan Siwei Tablets in treatment of chronic nephritis were screened, mainly including immune immune inflammatory factors PTGS2, NF-κB1, TNF, ALOX5, IL-6, MMP9; growth factors EGFR, VEGFA, HMOX1, TGFB1; apoptotic factors CASP3, CASP8, Bcl2, BAX; and kinases PIK3CA, Akt1, MAPK1. In addition, Shenyan Siwei Tablets in treatment of chronic nephritis by regulating the TNF, IL-17, HIF-1 and PI3K/Akt signaling pathways. The core active components of Shenyan Siwei Tablets were confirmed to have good docking activity with the targets of chronic nephritis by molecular docking. Conclusion The active components of Shenyan Siwei Tablets may play a role in the treatment of chronic nephritis by regulating targets and pathways related to inflammation, growth and apoptosis.

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省部共建中亚高发病成因与防治国家重点实验室开放课题（SKL-HIDCA-2022-32）；新疆维吾尔自治区自然科学基金资助项目（2022D01C744）