基于网络药理学与分子对接技术分析丹参治疗环孢素A肾毒性的作用机制
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Analysis of the Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in Treating Cyclosporine A Nephrotoxicity Based on Network Pharmacology and Molecular Docking Technology
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    摘要:

    目的:采用网络药理学联合分子对接技术分析丹参治疗环孢素A(CsA) 肾毒性的潜在作用机制。方法:通过中药系统药理学数据库(TCMSP) 检索丹参的活性成分,并联合TargetNet和SuperPred数据库预测其潜在作用靶点;利用GenCLiP 3和CTD数据库获取CsA肾毒性的相关疾病靶点。采用Venny 2.1.0工具分析丹参活性成分与CsA肾毒性的交集靶点。运用STRING数据库构建蛋白质互作(PPI) 网络,并借助Cytoscape软件进行可视化分析。通过DAVID数据库进行基因本体(GO) 功能及京都基因与基因组百科全书(KEGG) 通路富集分析。运用AutoDock Vina软件进行分子对接验证。结果:共筛选得到丹参33个活性成分及373个潜在作用靶点,CsA肾毒性疾病靶点760个,交集靶点100个。其中隐丹参酮、丹参酮IIA、丹参醇B、二氢丹参酮Ⅰ、黄芩苷和α-香树脂醇为主要活性成分,雌激素受体1(ESR1)、缺氧诱导因子1α(HIF1A)、热休克蛋白90αA1(HSP90AA1)、雷帕霉素机制性靶蛋白(MTOR)、核因子κB亚基1(NFKB1)、前列腺素内过氧化物合酶2 (PTGS2)、信号转导与转录激活因子1 (STAT1)、信号转导与转录激活因子3 (STAT3) 为核心靶点。GO富集分析共获得141个条目,包括68个生物过程、30个细胞组分及43个分子功能;KEGG富集分析揭示87条信号通路,主要涉及缺氧诱导因子-1(HIF-1)、磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)、凋亡和Toll样受体等信号通路。分子对接结果表明,丹参主要活性成分与核心靶点具有较强的结合亲和力。结论:丹参可能通过多成分协同调控多靶点、多通路的整合机制缓解CsA肾毒性。

    Abstract:

    Abstract:Objective:To analyze the potential mechanism of Salviae Miltiorrhizae Radix et Rhizoma in treating cyclosporine A (CsA) nephrotoxicity using network pharmacology combined with molecular docking technology. Methods: Active ingredients of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),and their potential targets were predicted using TargetNet and SuperPred databases. The CsA nephrotoxicity-related disease targets were obtained from GenCLiP 3 and CTD databases. The Venny 2.1.0 tool was used to analyze the intersecting targets between the active ingredients of Salviae Miltiorrhizae Radix et Rhizoma and CsA nephrotoxicity. The STRING database was employed to construct a protein-protein interaction (PPI) network, which was visualized using Cytoscape software. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database. Molecular docking validation was conducted using AutoDock Vina software. Results: A total of 33 active ingredients and 373 potential targets of Salviae Miltiorrhizae Radix et Rhizoma were screened, along with 760 CsA nephrotoxicity-related disease targets, resulting in 100 intersecting targets. Among these, cryptotanshinone, tanshinone IIA, danshenol B, dihydrotanshinone I, baicalin, and α -amyrin were identified as the main active ingredients, while estrogen receptor 1 (ESR1), hypoxia-inducible factor 1 alpha (HIF1A), heat shock protein 90 alpha family class A member 1 (HSP90AA1), mechanistic target of rapamycin kinase (MTOR), nuclear factor kappa B subunit 1 (NFKB1), prostaglandin-endoperoxide synthase 2 (PTGS2), signal transducer and activator of transcription 1 (STAT1), and signal transducer and activator of transcription 3 (STAT3) were identified as core targets. The GO enrichment analysis yielded 141 entries, including 68 biological processes,30 cellular components,and 43 molecular functions. The KEGG enrichment analysis revealed 87 signaling pathways, primarily involving hypoxia-inducible factor-1 (HIF-1), phosphatidylinositol 3-kinaseprotein kinase B (PI3K-Akt), apoptosis, and Toll-like receptor signaling pathways. Molecular docking results demonstrated strong binding affinities between the main active ingredients of Salviae Miltiorrhizae Radix et Rhizoma and the core targets. Conclusion: Salviae Miltiorrhizae Radix et Rhizoma may alleviate CsA nephrotoxicity through an integrated mechanism involving multiple ingredients synergistically regulating multiple targets and pathways.

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黄丽丽,罗广文,沈梦雅,汤柳.基于网络药理学与分子对接技术分析丹参治疗环孢素A肾毒性的作用机制[J].新中医,2026,58(9):148-156

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  • 在线发布日期: 2026-05-13
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