基于网络药理学的黄芪-水蛭药对治疗肺纤维化作用机制探析

目的:运用网络药理学方法研究黄芪-水蛭药对治疗肺纤维化(pulmonaryfibrosis,PF)的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、SwissADME、SwissTargetPrediction预测和筛选出黄芪和水蛭的活性成分及作用靶点。通过TTD、GeneCards、OMIM和DrugBank等数据库获取PF相关靶基因。采用Venny平台对药物靶基因和疾病靶基因映射筛选,得到黄芪-水蛭药对治疗PF的潜在靶标,进而用Cytoscape 3.7.2软件构建活性成分-靶点网络。通过STRING 10.0数据库和Cytoscape 3.7.2软件筛选并构建疾病靶点相互作用网络。采用DAVID数据库对黄芪-水蛭的作用靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路分析。结果:筛选出黄芪-水蛭药对潜在活性成分共60个,治疗PF的活性成分44个,作用靶点95个,关键靶点18个,涉及血管内皮生长因子受体、表皮生长因子受体、肿瘤坏死因子、白细胞介素-6、白细胞介素-1、基质金属蛋白酶等;潜在调控通路包括磷酯酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、肾素-血管紧张素(RAS)通路、丝裂原活化蛋白激酶(MAPK)信号通路、血管内皮生长因子(VEGF)信号通路、微小RNA信号通路、缺氧诱导因子-1(HIF-1)信号通路等;参与炎性反应、氧化应激、细胞凋亡和血管新生等多种生物过程。结论:黄芪-水蛭药对通过多成分、多靶点、多通路协调整合地发挥抗PF的作用,为后续细胞和动物实验提供参考。

Mechanism of Drug Pair Astragali Radix-Hirudo Against Pulmonary Fibrosis Based on Network Pharmacology

Objective To explore the mechanism of drug pair Astragali Radix-Hirudo in the treatment of pulmonary fibrosis (PF) based on the network pharmacology.Methods The active components and potential targets of Astragali Radix and Hirudo were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissADME, and SwissTargetPrediction. The potential genes related to PF were obtained from the Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), GeneCards, and DrugBank. The target genes of Astragali Radix-Hirudo were mapped with PF-related genes on the Venny platform to obtain the potential targets of Astragali Radix-Hirudo against PF. The component-target network was generated using Cytoscape 3.7.2. The protein-protein interaction (PPI) network was established using STRING 10.0 and visualized by Cytoscape 3.7.2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on candidate targets of Astragali Radix-Hirudo by DAVID.Results The network pharmacology revealed 60 active components of Astragali Radix and Hirudo, including 44 active components acting on 95 targets related to PF, and 18 targets were identified as core targets, involving vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1 (IL-1), and matrix metalloproteinases (MMPs). The pathway analysis indicated that many pathways were significantly enriched, for instance, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, renin-angiotensin system (RAS) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, VEGF signaling pathway, microRNA signaling pathway, and hypoxia-inducible factor 1 (HIF-1) signaling pathway. They were involved in various biological processes such as inflammatory response, oxidative stress, apoptosis, and angiogenesis.Conclusion Astragali Radix-Hirudo exhibits an anti-PF activity through multiple components, multiple targets, and multiple pathways in a coordinated and integrated matter. This study is expected to provide references for the subsequent research.