摘要
目的:采用网络药理学方法研究茵黄解毒汤治疗乙型肝炎病毒(hepatitis B virus,HBV)相关肝衰竭(hepatitis B virus related liver failure,HBV-LF)的活性成分及其分子机制。方法:采用GEO数据库筛选疾病相关差异基因(differentially expressed genes,DEGs),TCMSP数据库筛选中药复方小分子化合物及其作用靶点,Venny 2.1.0进行交集比对,确定交集靶点及其关系。运用Cytoscape构建茵黄解毒汤治疗HBV-LF的调控网络,Bisogenet构建蛋白互作网络(protein-protein interaction network,PPI),CytoNCA进行网络拓扑学分析。利用David数据库进行GO富集分析和KEGG信号通路富集分析。结果:本研究共得到HBV-LF的差异基因2160个,茵黄连解毒汤的药物靶点255个,交集靶点31个,相关小分子化合物66个。小分子化合物包括槲皮素、山柰酚、黄芩素、芦荟大黄素、黄连素等。PPI网络涉及55个关键节点,包括TP53、NTRK1、HSP90AA1、ESR1、CUL3、MCM2、CDK2、HSP90AB1、YWHAZ、NPM1、EGFR等。GO富集分析主要与细胞组分构成或来源、对刺激的反应、免疫过程、正/负调节的生物过程、细胞死亡、细胞增殖等有关。KEGG通路27条,主要涉及PI3K-Akt信号通路、MAPK信号通路、Cell cycle、Hepatitis B、自噬、FoxO信号通路、Ras信号通路、IL-17信号通路、NOD样受体信号通路、HIF-1信号通路、NF-κB信号通路等。结论:茵黄解毒汤拮抗HBVLF具有“多靶点-多通路-多作用”的特性,其作用机制可能与促进肝细胞增殖分化、降低肝细胞凋亡、调节机体免疫、抑制HBV复制等有关。
Objective:To study the active ingredients of Yinhuang Jiedu decoction in the treatment of hepatitis B virus(HBV)-related liver failure(HBV-LF)and its molecular mechanism using network pharmacology.Methods:GEO was used to screen DEGs,TCMSP database to sift small molecule compound of TCM compounds and the targets of action,Venny 2.1.0 to perform the intersection comparison,identifying intersecting targets and their relationships.Cytoscape was applied to build the regulation network of Yinhuang Jiedu decoction in the treatment of HBV-LF,Bisogenet to construct PPI,CytoNCA to perform network topology analysis.David database to conduct GO enrichment analysis and KEGG signaling pathway enrichment analysis.Results:The study gained 2160 DEGs of HBV-LF,255 targets of Yinhuang Jiedu decoction,31 intersecting targets and 66 relevant small molecular compounds.Small molecular compounds included quercetin,kaempferol,baicalein,aloe barbadensis,canthaxanthin,etc.PPI network involved 55 key links,covering TP53,NTRK1,HSP90AA1,ESR1,CUL3,MCM2,CDK2,HSP90AB1,YWHAZ,NPM1,EGFR and others.GO enrichment analysis is mainly connected with cellular component composition or the source,the response to the stimuli,immunologic process,biological process of positive/negative regulation,cellular death,cellular proliferation.All 27 KEGG pathways mainly refer to PI3K-Akt signal pathway,MAPK signaling pathway,Cell cycle,Hepatitis B,autophagy,FoxO signaling pathway,Ras signaling pathway,IL-17 signaling pathway,NOD-like receptor signaling pathway,HIF-1 signaling pathway and NF-κB signaling pathway.Conclusion:Yinhuang Jiedu decoction could treat HBV-LF from multi-target,multi-pathway and multi-effect,and its mechanism might be related to promoting the proliferation and differentiation of hepatocyte,reducing the apoptosis of hepatocyte,regulating body immunity and inhibiting the replication of HBV.
作者
曾胜澜
王娜
张荣臻
王挺帅
吴聪
毛德文
ZENG Shenglan;WANG Na;ZHANG Rongzhen;WANG Tingshuai;WU Cong;MAO Dewen(First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530023,China;Hunan University of Chinese Medicine,Changsha 410000,China;Guangxi University of Traditional Chinese Medicine,Nanning 530023,China)
出处
《西部中医药》
2024年第2期91-98,共8页
Western Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81960841,81774236,82060848)
国家中医药管理局“慢性重型肝炎解毒化瘀”重点研究室项目
广西自然科学基金(2020JJA140273)
广西中医药大学校级一般硕士研究生创新项目(YCSY2020011)。
关键词
网络药理学
茵黄解毒汤
乙型肝炎病毒
相关肝衰竭
network pharmacology
Yinhuang Jiedu decoction
hepatitis B virus
related liver failure
