摘要
目的基于网络药理学方法研究四君子汤治疗糖尿病的作用机制。方法借助TCMSP数据库及Uniprot数据库筛选出四君子汤有效成分及靶点基因。通过GeneCards数据库及OMIM数据库筛选出糖尿病的靶点基因,再用R语言将药物靶标基因与疾病靶标基因映射得到四君子汤作用于糖尿病的预测靶点,并用Cytoscape软件构建"药物-成分-靶点-疾病"相互作用网络图。将有效成分靶标与疾病靶标上传到STRING数据库,构建蛋白互作网络图(PPI),并在Cytoscape计算其度值(degree)及介数(Betweenness),并对得到的PPI进行核心基因的筛选。最后,运用R语言对关键靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果预测得到四君子汤治疗糖尿病的有效成分161个及"药物-疾病"共作有效靶点106个。PPI网络中筛选出的关键靶点有12个,分别为PRKCA、IL6、FOS、MAPK8、EGFR、CCND1、ESR1、NR3C1、RELA、NCOA1、AR、NCOA2。其中度值较高的有原癌基因(FOS)、表皮生长因子受体(EGFR)及雌激素受体(ESR1)等;生物功能的富集分析显示卡波西肉瘤相关疱疹病毒感染为显著性最高的通路,其主要涉及核转录因子-κB(NF-кB),胱天蛋白酶9(caspase-9,CASP9),血管内皮生长因子(VEGF),低氧诱导因子(HIF)等信号通路。结论基于网络药理学的研究表明,四君子汤治疗糖尿病是多成分、多靶点、多通路的复杂过程,主要通过参与细胞凋亡、氧化应激、炎症反应、内皮细胞增殖等发挥治疗糖尿病的作用。
Objective To study the mechanism of Sijunzi Decoction in the treatment of diabetes mellitus based on network pharmacology.Methods The effective components and target genes of Sijunzi Decoction were screened by TCMSP database and Uniprot database.The target genes of diabetes were screened by GeneCards database and OMIM database,and the target gene was mapped to the disease target gene by R language to obtain the predicted target of Sijunzi Decoction in diabetes,and the drug-component-target was constructed by Cytoscape software.The active component target and disease target were uploaded to the STRING database to construct a protein interaction network map(PPI),and the degree and Betweenness were calculated in Cytoscape,and the core gene was screened for the obtained PPI.Finally,the R target was used to perform gene ontology(GO)enrichment analysis and Kyoto Gene and Genomic Encyclopedia(KEGG)pathway enrichment analysis for key targets.Results A total of 161 active ingredients for the treatment of diabetes with Sijunzi Decoction and 106 effective targets for"drug-disease"were predicted.There were 12 key targets screened in the PPI network,namely PRKCA,IL6,FOS,MAPK8,EGFR,CCND1,ESR1,NR3 C1,RELA,NCOA1,AR,NCOA2.Among them,the values of proto-oncogene(FOS),epidermal growth factor receptor(EGFR)and estrogen receptor(ESR1)were higher.Enrichment analysis showed that Kaposi’s sarcoma-associated herpesvirus infection was the most significant pathway.It mainly involved nuclear transcription factor-κB(NF-кB),caspase-9(CASP9),vascular endothelial growth factor(VEGF),and hypoxia-inducible factor(HIF)signaling pathways.Conclusion Based on network pharmacology research,the treatment of diabetes with Sijunzi Decoction is a multi-component,multi-target,multi-channel complex process,which is mainlyby participating in apoptosis,oxidative stress,inflammatory reaction and endothelial cell proliferation to achieve the effect.
作者
申鑫惠
杨宇峰
石岩
SHEN Xinhui;YANG Yufeng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)
出处
《中华中医药学刊》
CAS
北大核心
2020年第6期37-41,I0013-I0015,共8页
Chinese Archives of Traditional Chinese Medicine
基金
国家科技支撑计划(2014BAI10B04)。
作者简介
申鑫惠(1996-).女,辽宁大连人,硕士研究生,研究方向:中医内科学内分泌;通讯作者:石岩(1963-).男,辽宁沈阳人,教授,博士研究生导师,博士,研究方向:中医内科学的临床与科研。
