基于网络药理学与分子对接技术分析参附注射液治疗脓毒症相关急性肾损伤作用机制
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R285

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浙江省基础公益研究计划项目(LTGY23H150001);台州市社会发展科技计划项目(24ywb149);温岭市社会发展科技计划项目(2024S00264)


Analysis of Mechanism of Shenfu Injection in the Treatment of Sepsis-Associated Acute Kidney Injury Based on Network Pharmacology and Molecular Docking Technology
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    摘要:

    目的:基于网络药理学与分子对接技术分析参附注射液治疗脓毒症相关急性肾损伤的作用机制。 方法:使用中药系统药理学数据库及分析平台(TCMSP) 预测参附注射液的作用靶点,同时从GeneCards、 OMIM、PharmGkb、TTD、Disgenet数据库筛选脓毒症急性肾损伤相关靶点,经数据整合取交集,确定参附注 射液调控该病症的潜在靶点;使用Cytoscape3.8.0软件构建“药物-成分-靶点”网络;使用STRING数据库构建 关键靶点蛋白质互作(PPI) 网络;利用R语言对治疗靶点进行基因本体(GO) 功能和京都基因与基因组百科 全书(KEGG) 通路富集分析;并进行分子对接验证。结果:获得参附注射液活性成分89个,对应靶点89个, 获得脓毒症相关急性肾损伤疾病靶点4 017 个,药物疾病交集靶点61 个,其中核心靶点为雌激素受体 1(ESR1)、白细胞介素(IL) -6、肿瘤坏死因子(TNF)、IL-1β、肿瘤蛋白p53(TP53)、前列腺素内过氧化 物合酶2(PTGS2)、半胱天冬酶-3(CASP3)、B细胞淋巴瘤-2(BCL-2)。主要活性成分为β-谷甾醇、人参皂 苷Rh2、β-榄香烯、棕榈酸、四氢异喹啉醇。KEGG分析涉及细胞凋亡、磷脂酰肌醇3激酶(PI3K) -蛋白激酶 B(Akt)、TNF及IL-17等关键信号通路。分子对接结果显示人参皂苷Rh2与CASP3、TNF、PTGS2均有较好的 结合能力。结论:参附注射液通过多成分、多靶点、多通路协同作用,发挥减轻炎症风暴、抑制细胞凋亡、改 善氧化应激等作用以治疗脓毒症相关急性肾损伤。

    Abstract:

    Abstract:Objective:To analyze the mechanism of Shenfu Injection in the treatment of sepsis-associated acute kidney injury( SA-AKI) based on network pharmacology and molecular docking technology. Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to predict the potential targets of Shenfu Injection. Disease targets for SA-AKI were retrieved from The Human Gene Database (GeneCards), Online Mendelian Inheritance in Man( OMIM),Pharmacogenetics and Pharmacogenomics Knowledge Base( PharmGKB), Therapeutic Target Database (TTD),and DisGeNET databases. Overlapping targets between Shenfu Injection and SAAKI were identified to determine the potential therapeutic targets of Shenfu Injection for this condition. Cytoscape 3.8.0 software was used to construct a "drug-component-target" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to establish a protein-protein interaction (PPI) network of the key targets. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the therapeutic targets using R language. Molecular docking verification was also conducted. Results: A total of 89 active components and 89 corresponding targets of Shenfu Injection were obtained. There were 4 017 disease targets related to SA-AKI, resulting in 61 overlapping drug-disease targets. The core targets included estrogen receptor 1 (ESR1),interleukin (IL)-6,tumor necrosis factor (TNF),IL-1β,tumor protein p53 (TP53),prostaglandin-endoperoxide synthase 2 (PTGS2),caspase-3 (CASP3),and B-cell lymphoma 2 (BCL-2). The main active components were β-sitosterol, ginsenoside Rh2, β-elemene, palmitic acid, and salsolinol. KEGG pathway analysis involved key signaling pathways such as apoptosis, phosphatidylinositol-3- kinase (PI3K)/protein kinase B (Akt), TNF, and IL-17. Molecular docking results indicated good binding affinity between ginsenoside Rh2 and CASP3,TNF,and PTGS2. Conclusion:Shenfu Injection exerts its therapeutic effects on SA-AKI through a multi-component, multi-target, and multi-pathway synergistic mechanism, including mitigating the cytokine storm,inhibiting cell apoptosis,and ameliorating oxidative stress.

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叶亚平,宋于康,彭晨,柯军中,钟丹锋.基于网络药理学与分子对接技术分析参附注射液治疗脓毒症相关急性肾损伤作用机制[J].新中医,2026,58(5):166-172

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  • 在线发布日期: 2026-03-12
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