基于网络药理学和分子对接分析麦角固醇治疗 脓毒症相关急性肺损伤的作用机制

To Analyze the Mechanisms of Ergosterol in the Treatment of Sepsis-Induced Acute Lung Injury Based on Network Pharmacology and Molecular Docking

摘要: 目的：通过网络药理学和分子对接技术，分析麦角固醇治疗脓毒症相关急性肺损伤(sepsis induced acute lung injury, SI-ALI)的潜在靶点和作用机制。方法：通过PharmMapper、Stitch、TCMSP、Herb、SEA 数据库收集麦角固醇的药物靶点，在GeneCards、OMIM、TTD数据库筛选脓毒症和急性肺损伤相关疾病靶点，利用Venny 2.1.0平台提取三者交集靶点，运用STRING平台构建交集靶点的蛋白相互作用(PPI)网络，预测核心靶点，通过Metascape数据库对交集靶点进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。由Auto Dock软件进行分子对接，利用PyMOL将分子对接结果进行可视化处理。结果：本研究共筛选出327个麦角固醇相关靶点，9876个急性肺损伤相关靶点以及3804个脓毒症相关靶点，三者取交集共得到159个关键靶点。经过二次筛选后确定四个核心靶点(AKT1, NFKB1, STAT3, IFNG)。GO/KEGG富集分析显示，这些靶点显著富集于炎症反应调控、细胞分解代谢、类固醇代谢等生物学过程，麦角固醇可能通过凋亡、脂质与动脉粥样硬化、PI3K-Akt信号通路、HIF-1信号通路等通路治疗SI-ALI。分子对接结果显示麦角固醇与AKT1、NFKB1、STAT3、IFNG等核心靶点具有较强的结合能力。结论：麦角固醇可能通过多成分、多靶点、多途径治疗SI-ALI，我们初步探究了麦角固醇治疗SI-ALI的有效成分和分子机制，并通过分子对接进行初步验证。

Abstract: Objective: The potential targets and mechanisms of ergosterol in the treatment of sepsis-induced acute lung injury (SI-ALI) were analyzed through network pharmacology and molecular docking technology. Methods: The drug targets of ergosterol were collected by PharmMapper, Stitch, TCMSP, Herb and SEA databases. The drug targets of ergosterol were collected by PharmMapper, Stitch, TCMSP, Herb and SEA databases. The targets of sepsis and acute lung injury were screened in GeneCards, OMIM and TTD databases. Venny 2.1.0 platform was used to extract the intersection targets. STRING platform was used to construct the protein-protein interaction (PPI) network of the intersection targets to predict the core targets. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersection targets through the Metascape database. The molecular docking was performed by Auto Dock software, and the molecular docking results were visualized by PyMOL. Results: A total of 327 ergosterol-related targets, 9876 acute lung injury-related targets and 3804 sepsis-related targets were screened in this study. A total of 159 key targets were obtained from the intersection. Four core targets (AKT1, NFKB1, STAT3, IFNG) were identified after two screenings. GO/KEGG enrichment analysis showed that these targets were significantly enriched in biological processes such as inflammatory response regulation, cell catabolism, and steroid metabolism. Ergosterol may treat SI-ALI through signaling pathways such as apoptosis, lipid and atherosclerosis, PI3K-Akt, and HIF-1. Molecular docking results showed that ergosterol had strong binding ability with AKT1, NFKB1, STAT3, IFNG. Conclusions: Ergosterol may treat SI-ALI through multi-component, multi-target and multi-pathway. We preliminarily explored the effective components and molecular mechanism of ergosterol in the treatment of SI-ALI, and preliminarily verified by molecular docking.