基于网络药理学探讨热毒宁注射液治疗登革热的分子机制

Exploration of Molecular Mechanism of Reduning Injection in the Treatment of Dengue Fever Based on Network Pharmacology

【目的】基于网络药理学探讨热毒宁注射液治疗登革热的分子机制。【方法】收集文献报道的热毒宁注射液活性成分,并通过瑞士靶点预测(SwissTargetPrediction)数据库预测上述成分的作用靶点;通过人类基因数据库(GeneCards)、人类孟德尔遗传在线数据库(OMIM)、治疗靶点数据库(TTD)、比较毒理学数据库(CTD)收集登革热的主要靶点;取药物-疾病交集靶点,利用STRING数据库和Cytoscape 3.7.1软件构建关键靶点蛋白-蛋白相互作用(PPI)网络,根据关键靶点网络节点度值筛选出关键药效成分;将交集靶点上传至Metascape平台进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,结合文献调研及关键靶点筛选出关键通路。【结果】热毒宁注射液共有31个活性成分作用于154个登革热靶点,依据节点度值筛选出29个关键靶点,并由此筛选出8个关键活性成分;GO和KEGG富集分析分别得到1 501个、142个条目,筛选出5条关键通路。【结论】热毒宁注射液治疗登革热可能通过作用GAPDH、AKT1、TNF、MAPK、CASP-3等关键靶点,调节缺氧诱导因子1(HIF-1)信号通路、核因子kappaB(NF-κB)信号通路、白细胞跨内皮迁移、黏附连接和线粒体自噬等关键信号通路,发挥抗病毒、抗炎、调节免疫、调节凝血和纤溶、调节能量代谢、调节脂质代谢等作用。

Objective To explore the molecular mechanism of Reduning Injection in treating dengue fever based on network pharmacology. Methods The active constituents of Reduning Injection reported in literatures were collected,and the targets of the above constituents were predicted by SwissTargetPrediction database. The main targets of Dengue fever were collected by GeneCards, Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),and the Comparative Toxicogenomics Database(CTD). The targets of drugdisease intersection were achieved to construct the protein-protein interaction(PPI) network using STRING database and Cytoscape 3.7.1 software, and then the key pharmacodynamic components were screened out according to the node degree value of the PPI network. The obtained intersection targets were uploaded to Metascape platform for analysis of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG),and then the key pathways were screened out by literature research and key targets. Results There were 31 active constituents in Reduning Injection acting on 154 dengue fever targets. According to node degree,29 key targets were screened out,and 8 key active constituents were obtained. GO and KEGG enrichment analysis results showed1 501,142 items,and 5 key pathways. Conclusion The treatment of dengue fever with Reduning injection plays a role in anti-virus, anti-inflammation, immune regulation, coagulation and fibrinolysis regulation, energy metabolism regulation and lipid metabolism regulation through acting on possible key targets such as GAPDH,AKT1, TNF, MAPK and CASP-3, and regulating hypoxia-inducible factor 1(HIF-1)signaling pathway,nuclear factor-kappaB(NF-κB)signaling pathway,leucocyte transendothelial migration,adhesion junctions and mitochondrial autophagy.