基于网络药理学的葛根芩连汤治疗腹泻作用机制研究

Mechanism of Gegen Qinlian decoction on diarrhea based on network pharmacology

目的:以网络药理学为载体探索葛根芩连汤治疗腹泻的基因靶点及作用通路。方法:初步检索中药系统药理学数据库与分析平台,查找目标中药的有效成分和基因靶点,定义生物利用度≥30%,类药性≥0.18,确定药物的作用靶点;然后查询OMIM、DisGeNET、GeneCards数据库,挖掘腹泻疾病的潜在靶点。最后对两种基因取交集,构建中药—成分—靶基因—疾病的中药调控网络,对网络里面的基因构建蛋白互作网络,找到核心基因,进行基因本体和京都基因与基因组百科全书分析。结果:最终确定葛根芩连汤中有效成分总共486个,去除重复后获得有效成分121个,基因靶点221个;腹泻的疾病靶点5217个,二者共同靶点基因182个,PPI网络蛋白分析发现AKT1、CASP3、JUN、PTGS2、RELA、ESR1是葛根芩连汤治疗腹泻的核心靶点。基因本体分析确定了157个条目(P<0.05),其中生物过程主要通过DNA、RNA的转录,细胞因子的结合,蛋白酶的激活及细胞的代谢等过程发挥作用;京都基因与基因组百科全书通路富集分析明确了167条信号通路,其中信号通路涉及炎症、细胞代谢、细胞衰老等方面,主要IL-17信号通路、TNF信号通路、HIF-1信号通路等。结论:葛根芩连汤对腹泻的治疗主要通过抗炎、缓解肌肉痉挛等机制发挥作用;其具体分子机制尚未得到验证,后期需要借助分子生物学研究,完善葛根芩连汤的作用机制,为临床用药提供新依据。

Objective:Use network pharmacology as a carrier to explore the gene targets and pathways of Gegen Qinlian decoction in the treatment of diarrhea.Methods:Preliminarily search the Chinese medicine system pharmacology database and analysis platform,find the effective ingredients and gene targets of the target Chinese medicine,define the bioavailability≥30%,the drug-like property≥0.18,and determine the target of the drug;then,query OMIM,DisGeNET,GeneCards database,mining potential targets of diarrhea diseases.Finally,take the intersection of the two genes to construct a traditional Chinese medicine-component-target gene-disease regulatory network,construct a protein interaction network for the genes in the network,find the core genes,and analyze the gene ontology and the Kyoto Encyclopedia of Genes and Genomes.Results:The results finally determined that there are a total of 486 active ingredients in Gegen Qinlian decoction,121 active ingredients and 221 gene targets are obtained after removing duplication;5217 disease targets for diarrhea,182 common target genes for the two,PPI network protein analysis.It is found that AKT1,CASP3,JUN,PTGS2,RELA,ESR1 are the core targets of Gegen Qinlian decoction in the treatment of diarrhea.Gene ontology analysis identified 157 items(P<0.05).Among them,biological processes mainly play a role in the transcription of DNA and RNA,the binding of cytokines,the activation of proteases and the metabolism of cells;the Kyoto Encyclopedia of Genes and Genomes pathways are rich Collective analysis identified 167 signal pathways,of which the signal pathways involve inflammation,cell metabolism,cell aging,etc.The main IL-17 signal pathway,TNF signal pathway,and HIF-1 signal pathway.Conclusion:Gegen Qinlian decoction has the advantages of multiple targets and multiple pathways.The treatment of diarrhea is mainly through anti-inflammatory and relieving muscle spasm.The specific molecular mechanism of Gegen Qinlian decoction has not been verified,and it needs to be used in the later stage.Molecular biology research has perfected the mechanism of Gegen Qinlian decoction and provided a new basis for clinical medication.