[关键词]
[摘要]
目的 基于数据挖掘、网络药理学、分子对接以及细胞实验探讨中药复方治疗特发性膜性肾病(IMN)的用药规律和作用机制。方法 在中国学术期刊全文数据库(CNKI)、维普期刊(VIP)、万方数据知识服务平台(Wanfang Data)、PubMed数据库中检索中药复方治疗IMN的相关文献,统计中药使用频次,进行性味归经统计、关联规则分析、聚类分析,筛选核心药物。通过网络药理学获取核心药物的活性成分及靶点,与IMN疾病靶点取交集,构建蛋白质-蛋白质相互作用(PPI)网络,进行基因本体(GO)注释及京都基因与基因组百科全书(KEGG)通路富集分析。通过分子对接验证活性成分与关键靶点的结合能力,并利用体外细胞实验验证玉兰脂素B的保护作用及机制。结果 共纳入221篇文献、160个处方、186种中药。核心药物组合“薏苡仁、苍术、白花蛇舌草、党参、山药、丹参”通过108个活性成分作用于307个交集靶点,富集于晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)、磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)等信号通路。分子对接显示玉兰脂素B、2-hydroxyisoxypropyl-3-hydroxy-7-isopentene-2,3-dihydrobenzofuran-5-carboxylic、槲皮素等与AKT1、肿瘤蛋白p53(TP53)、信号转导因子和转录激活因子3(STAT3)、肿瘤坏死因子(TNF)结合良好。CCK-8、Western blotting、Annexin V-FITC/PI流式细胞术等实验证实玉兰脂素B能通过调控PI3K/Akt通路抑制足细胞凋亡,增强细胞活力。结论 核心药物可能通过多成分、多靶点、多通路参与IMN治疗,体外实验为网络药理学预测提供了实验验证。
[Key word]
[Abstract]
Objective To explore the mechanisms and medication rules of traditional Chinese medicine(TCM) for idiopathic membranous nephropathy(IMN) using data mining, network pharmacology, molecular docking, and cellular experiments. Methods Literature on TCM for IMN was retrieved from China National Knowledge Infrastructure(CNKI), VIP, Wanfang Data, and PubMed. Herb frequencies, properties, association rules, and clustering analyses were performed to identify core herbs. Active components and targets of core herbs were obtained via network pharmacology. Protein-protein interaction(PPI) networks were constructed, and gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was conducted. Molecular docking was used to verify the binding ability of active components with key targets, and in vitro cell experiments were conducted to validate the protective effect and mechanism of denudatin B. Results A total of 221 articles, 160 prescriptions, and 186 herbs were included. The core herbal combination acted via 108 active components on 307 overlapping targets, enriched in AGE-RAGE and PI3K-Akt pathways. Molecular docking showed stable binding between denudatin B, 2-hydroxyisoxypropyl-3-hydroxy-7-isopentene-2,3-dihydrobenzofuran-5-carboxylic, quercetin, and TP53, STAT3, AKT1, TNF. In vitro, denudatin B inhibited podocyte apoptosis and enhanced viability via PI3K/Akt pathway. Conclusion Core herbs may treat IMN via multi-component, multi-target, and multi-pathway mechanisms, supported by experimental validation.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金面上项目(82574958); 中医证候全国重点实验室项目(QZ2025ZZ32); 省部共建中医湿证国家重点实验室专项(SZ2021ZZ09,SZ2021ZZ36); 广州市科技计划项目(2025A03J4062,2025A03J3150); 广东省中医院院内专项(YN2024MS019,YN2024MS033)