基于网络药理学的热毒宁注射液治疗手足口病作用机制研究

Study on the mechanism of Reduning injection in the treatment of hand,foot and mouth disease based on network pharmacology

目的初步探索热毒宁注射液治疗手足口病的作用机制。方法通过文献的检索与整合得到热毒宁注射液的化合物成分,检索SwissTargetPrediction,STITCH与SuperPred数据库得到热毒宁注射液化合物靶点数据集;通过GeneCards与DiGSeE数据库检索疾病相关靶点;使用Cytoscape软件进行化合物-靶点与疾病-靶点网络作图;通过STRING数据库对潜在靶点进行PPI网络分析;利用R软件对潜在靶点和PPI聚类分析得到的两个模块进行GO功能与KEGG通路富集分析并可视化;最后应用AutoDockTools-1.5.6软件对重要化合物进行分子对接预测。结果热毒宁注射液化合物-靶点-手足口病网络中包含215个点944条边,度值最高的十个靶点为MMP2、CA6、MMP13、ELANE、MMP1、MMP9、EGFR、TYR、ABCB1和APP。潜在靶点的PPI网络图共包含122个点和938条边,其中,度值最高的十个靶点为AKT1、MAPK1、VEGFA、IL6、STAT3、TP53、IGF1、EGFR、HRAS和TNF。通过对潜在靶点的GO和KEGG富集分析,共得到3542条GO功能条目和147条KEGG通路。GO功能条目中,包括3128条生物过程(BP)相关条目,251条分子功能(MF)相关条目和163条细胞成分(CC)相关条目。分子对接结果验证了热毒宁注射液化合物与靶点的结合能力,尤其是MAPK1、AKT1、TP53的靶点。结论本研究通过网络药理学方法初步预测并验证了热毒宁注射液治疗手足口病的作用机制,并通过分子对接技术进行了验证,为进一步开展相关实验研究奠定了基础。

Objective Preliminarily explore the mechanism of Reduning injection in the treatment of hand,foot and mouth dis-ease.Methods Search for disease-related targets through GeneCards and DiGSeE databases,use Cytoscape software to map compound-target and disease-target networks,use STRING database to perform PPI network analysis on potential targets,use R software to analyze potential targets and The two modules obtained by PPI cluster analysis are used for GO function and KEGG pathway enrichment analysis and visualization.Finally,AutoDockTools-1.5.6 software was used to predict the molecular doc-king of important compounds.Results Reduning injection compound-target-hand-foot-mouth disease network contains 215 points and 944 edges.The ten targets with the highest degree are MMP2,CA6,MMP13,ELANE,MMP1,MMP9,EGFR,TYR,ABCB1 and APP.The PPI network diagram of potential targets contains 122 points and 938 edges.The ten targets with the highest degree are AKT1,MAPK1,VEGFA,IL6,STAT3,TP53,IGF1,EGFR,HRAS and TNF.Through the GO and KEGG enrichment analysis of potential targets,we obtained a total of 3542 GO function entries and 147 KEGG pathways.Among the GO function items,there are 3128 items related to biological process(BP),251 items related to molecular function(MF)and 163 i-tems related to cell component(CC).The molecular docking results verified the binding ability of Reduning injection compound to the target,especially the targets of MAPK1,AKT1,and TP53.Conclusion This study preliminarily predicted and verified the mechanism of Reduning injection in the treatment of hand-foot-mouth disease through network pharmacology,and verified it through molecular docking technology,laying a foundation for further relevant experimental research.