基于网络药理学探讨灯盏细辛治疗阿霉素心肌损伤的作用机制

Mechanism of dengzhanxixin injection in the treatment of doxorubicin-induced myocardial injury based on network pharmacology

目的采用网络药理学方法探讨灯盏细辛注射液治疗阿霉素心肌损伤的相关作用机制。方法采用TCMSP数据库分析灯盏细辛的活性成分及作用靶点,采用Disgenet、OMIM、GeneCards、Phenopedia、Phenolyzer数据库分析阿霉素心肌损伤相关靶点,将灯盏细辛注射液作用靶点与阿霉素心肌损伤靶点取交集,获取交集靶点。采用CytoNCA软件构建灯盏细辛活性成分-阿霉素心肌损伤靶点网络图,利用STRING软件绘制PPI网络图,采用DAVID软件进行KEGG通路分析和GO富集分析。结果筛选获得43个灯盏细辛注射液活性成分,对应靶点188个,疾病靶点494个,灯盏细辛注射液与阿霉素心肌损伤的交集靶点75个。GO富集分析得到GO条目30个,其中分子功能10个,生物过程条目10个,细胞组成条目10个。KEGG通路分析获得具有统计学意义的信号通路20条(P<0.05),涉及TNF信号通路,IL-17信号通路,AGE-RAGE信号通路等。并采用ELISA验证灯盏细辛可降低阿霉素诱导心肌H9C2细胞炎症因子IL-6和TNF-的上调对心肌细胞发挥保护作用(P<0.001)。结论应用网络药理学方法阐明了灯盏细辛注射液治疗阿霉素心肌损伤的作用靶点及通路,为灯盏细辛治疗阿霉素心肌损伤提供了理论与实验依据。

Objective Explore the relevant mechanism of Dengzhanxixin injection in the treatment of doxorubicin-induced myocardial injury using network pharmacology methods.Methods The TCMSP database was used to analyze the active ingredients and targets of Dengzhanxixin injection.Disgene,OMIM,GeneCards,Phenomedia,and Phenolyzer databases were used to analyze targets related to doxorubicin myocardial injury.The intersection of Dengzhanxixin injection targets and doxorubicin myocardial injury targets was obtained to obtain the intersection targets.Using CytoNCA software to construct a network diagram of the active ingredient of Dengzhanxixin-doxorubicin-induced myocardial injury target,using STRING software to draw a PPI network diagram,and using DAVID software for KEGG pathway analysis and GO enrichment analysis.Results 43 active ingredients of Dengzhanxixin injection were selected,corresponding to 188 targets,494 disease targets and 75 intersection targets of Dengzhanxixin injection and doxorubicin-induced myocardial injury.There were 30 GO entries,including 10 molecular functions,10 biological process entries,and 10 cell composition entries based on GO enrichment analysis.The analysis of the KEGG pathway obtained 20 statistically significant signaling pathways(P<0.05),involving the TNF signaling pathway,the IL-17 signaling pathway,the AGE-RAGE signaling pathway,etc.And ELISA was used to verify that Dengzhanxixin can reduce the up-regulation of doxorubicin-induced inflammatory factors IL-6 and TNF-αinduced by doxorubicin in H9C2 myocardial cells,exerting a protective effect on myocardial cells(P<0.001).Conclusions The application of network pharmacology methods has elucidated the target and pathway of Dengzhanxixin injection in the treatment of doxorubicin-induced myocardial injury,providing a theoretical and experimental basis for Dengzhanxixin in the treatment of doxorubicin-induced myocardial injury.