基于网络药理学探讨当归补血汤治疗化疗所致心肌损伤的机制

The Mechanism of Danggui Buxue Decoction in Treating Myocardial Injury Caused by Chemotherapy Based on Network Pharmacology

目的基于网络药理学探讨当归补血汤治疗化疗所致心肌损伤的可能作用机制。方法通过检索中药系统药理学技术平台(TCMSP)数据库筛选出黄芪、当归的潜在活性成分及靶点,采用人类基因数据库(GeneCards)、人类孟德尔遗传数据库(OMIM)、治疗靶点数据库(TTD)、药物数据库(DrugBank)获得心肌损伤的作用靶点,得到药物与疾病的交集靶点,并运用CytoScape 3.7.2软件绘制活性成分-靶点-疾病交互网络图。采用STRING数据库构建靶点蛋白-蛋白相互作用(PPI)网络,并应用R软件进行统计分析,使用R软件对交集靶点进行基因本体(GO)功能分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选出当归补血汤的潜在活性成分59个、靶点707个,心肌损伤相关靶点2943个,药物与疾病的交集基因靶点157个,涉及的有效成分47个。筛选出109个PPI核心基因,GO功能富集显示靶点主要参与肾上腺素受体活性、类固醇激素受体活性、G蛋白偶联的胺受体活性、核受体活性等生物过程。KEGG通路富集显示当归补血汤主要参与磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、丝裂原活化蛋白激酶(MAPK)、白细胞介素17(IL-17)、肿瘤坏死因子(TNF)、缺氧诱导因子1(HIF-1)等信号通路。结论基于网络药理学研究显示,当归补血汤治疗心肌损伤具有多成分、多靶点、多通路的作用机制特点,可为探讨中医药治疗化疗所致心肌损伤的机制提供参考。

Objective To explore the mechanism of Danggui Buxue Decoction in treating myocardial injury caused by chemotherapy based on network pharmacology.Methods The potential active ingredients and targets of Astragalus and Angelica were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database.The targets of myocardial injury were obtained by using Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD)and DrugBank databases.The intersection targets of drugs and diseases were obtained.CytoScape 3.7.2 software was used to map the active component-target-disease interaction network.The protein-protein interaction(PPI)network of target interaction was constructed using STRING database and statistical analysis was performed by R software.Gene Ontology(GO)analysis and pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed by R software for intersection targets.Results A total of 59 potential active ingredients,707 targets of Danggui Buxue Decoction,2943 targets related to myocardial injury,157 gene targets of drug and disease intersection,and 47 active ingredients were screened out.A total of 109 PPI core genes were screened,and GO function enrichment showed that the targets were mainly involved in biological processes such as adrenaline receptor activity,steroid hormone receptor activity,G protein-coupled amine receptor activity,and nuclear receptor activity.The enrichment of KEGG pathway showed that Danggui Buxue Decoction was mainly involved in the signal pathways of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),mitogen-activated protein kinase(MAPK),interleukin 17(IL-17),tumor necrosis factor(TNF),hypoxia inducible factor 1(HIF-1).Conclusion Based on network pharmacology,Danggui Buxue Decoction in treating myocardial injury caused by chemotherapy might relate to multi-components,multi-targets and multi-pathways,which could provide references for exploring the mechanism of treating chemotherapy-induced myocardial injury with traditional Chinese medicine.