基于网络药理学与GEO数据库探讨心瘅方治疗病毒性心肌炎的机制  

Exploration into the Mechanism of Xindan Formula(Heart-heat Formula)in the Treatment of Viral Myocarditis based on Network Pharmacology and GEO Database

作　　者：张平安 高娜 姚涛[2] 王国斌[3] 车志英[2] ZHANG Ping'an;GAO Na;YAO Tao;WANG Guobin;CHE Zhiying(Beijing University of Chinese Medicine,Beijing 100029,China;Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China;Third Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450003,China)

机构地区：[1]北京中医药大学,北京100029 [2]河南中医药大学,河南郑州450046 [3]河南中医药大学第三附属医院,河南郑州450003

出　　处：《西部中医药》2024年第5期101-109,共9页Western Journal of Traditional Chinese Medicine

基　　金：国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医人教发[2016]42号);2020年河南中医药大学重点学科建设项目(15102044-2020-2)。

摘　　要：目的:基于网络药理学与GEO数据库探讨心瘅方治疗病毒性心肌炎的microRNA-mRNA调控机制。方法:使用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选心瘅方中药物活性成分及其靶基因;利用GEO数据库筛选病毒性心肌炎与健康人的差异microRNA;利用FunRich3.1.3对差异microRNA进行mRNA富集,并与药物靶基因取交集基因;通过蛋白-蛋白互作网络(protein-protein interactions,PPI)以及cytoNCA筛选出核心基因;运用R软件对核心基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果:心瘅方中药物活性成分共199个,潜在作用靶点490个,GEO数据库Series GSE148153符合要求,通过筛选得到差异microRNA 438个,50个microRNA与核心基因有对应关系,上调基因45个,下调基因5个;筛选得到交集基因207个,其中33个为核心基因;GO功能注释主要富集在肌细胞增殖、MAP激酶活性等生物学过程,并且主要富集在PI3K/Akt、人巨细胞病毒感染、白细胞介素17等信号通路。结论:心瘅方调控microRNA-mRNA过程治疗病毒性心肌炎与中药成分干预肌细胞增殖、MAP激酶活性等生物学过程和PI3K/Akt、人巨细胞病毒感染、肿瘤坏死因子信号通路等有关,此过程可能涉及hsa-miR-15b-5p和hsa-miR-21-5p等外泌体的表达。Objective:To investigate the microRNA-mRNA regulatory mechanism of Xindan formula(heart-heat formula)in the treatment of viral myocarditis based on network pharmacology and GEO database.Methods:The TCMSP database was used to screen the active ingredients of the drugs and their target genes;the GEO database was utilized to search for differential microRNAs between viral myocarditis and healthy individuals;FunRich 3.1.3 was applied to perform mRNA enrichment of the differential microRNAs and take the intersecting genes with the target genes of the drugs;the core genes were screened by the PPI as well as cytoNCA;and the core genes were analyzed by GO and KEGG pathway enrichment using the R software.Results:There were 199 active ingredients and 490 potential targets in the herbs of Xindan formula,and the GEO database Series GSE148153 met the requirements.438 differential microRNAs were obtained through screening,50 microRNAs had correspondence with core genes,45 up-regulated genes and five down-regulated genes;207 intersecting genes were obtained through screening,33 of which were core genes;GO functional annotations were mainly enriched in biological processes such as myoblast proliferation,MAP kinase activity,and mainly enriched in PI3K-Akt signaling pathway,human cytomegalovirus infection,and IL-17 signaling pathway.Conclusion:The process of Xindan formula regulating the microRNA-mRNA in the treatment of viral myocarditis is related to the intervention of herbal ingredients in biological processes such as myocyte proliferation,MAP kinase activity and PI3K-Akt,human cytomegalovirus infection,and tumor necrosis factor signaling pathway,etc.,and this process may involve the expression of exosomes,such as hsa-miR-15b-5p and hsa-miR-21-5p,etc.

关 键 词：病毒性心肌炎 网络药理学 GEO数据库 靶基因 MICRORNA 心瘅方 

分 类 号：R256.21[医药卫生—中医内科学]