基于网络药理学探讨大黄治疗儿童功能性便秘的作用机制研究

Study on the Mechanism of Rhubarb in the Treatment of Functional Constipation in Children Based on Network Pharmacology

目的:采用网络药理学探讨大黄治疗儿童功能性便秘(FC)的作用机制。方法:通过TCMSP数据库获取大黄的主要活性成分和作用靶点,利用Genecards数据库检索出FC的潜在靶点,再筛选以上两者的共同靶点,获得靶蛋白之间的相互作用关系,采用Cytoscape3.7.2软件绘制“大黄-活性成分-靶点-FC”相互作用网络图,最后对交集靶点进行蛋白互作网络(PPI)分析,GO功能分析和KEGG通路富集分析。结果:收集到大黄有效活性成分16个,所对应基因靶点37个,FC基因靶点4521个,大黄和FC共同交集靶点为26个。PPI结果显示:大黄中的CASP3、MYC、ESR1、HSP90AA1、CCNB1、CASP8等为治疗FC的核心靶点。GO功能分析显示靶点基因主要富集于对类固醇激素的反应、对雌二醇的反等。KEGG通路富集分析主要包括化学致癌作用-受体激活、乙型肝炎、人类免疫缺陷病毒1型感染、脂质和动脉粥样硬化信号通路、PI3K-Akt信号通路、神经退行性疾病信号通路、p53信号通路、胆碱能突触和雌激素信号通路等对FC产生治疗作用。结论:大黄通过多成分、多靶点和多通路治疗FC,但其机制仍需进一步体内体外实验证实。

Objective:To explore the mechanism of rhubarb in the treatment of functional constipation(FC)in children by network pharmacology.Methods:The main active components and action targets of rhubarb were obtained through TCMSP database,the potential targets of FC were retrieved by Genecards database,and then the common targets of the above two were screened to obtain the interaction relationship between target proteins.The interaction network diagram of"rhubarbactive components-target-FC"was drawn by Cytoscape3.7.2 software.Finally,the intersection targets were analyzed by protein-protein interaction network(PPI),GO function and KEGG pathway enrichment.Results:Sixteen active components of rhubarb were collected,37 corresponding gene targets,4521 FC gene targets and 26 common intersection targets of rhubarb and FC were collected.PPI results showed that CASP3,MYC,ESR1,HSP90AA1,CCNB1 and CASP8 in rhubarb were the core targets for the treatment of FC.GO functional analysis showed that the target genes were mainly concentrated in the response to steroids and estradiol.KEGG pathway enrichment analysis mainly includes chemical carcinogenesis receptor activation,hepatitis B,human immunodeficiency virus type 1 infection,lipid and atherosclerosis signal pathway,PI3K-Akt signal pathway,neurodegenerative disease signal pathway,p53 signal pathway,cholinergic synapse and estrogen signal pathway had therapeutic effect on FC.Conclusion:Rhubarb can treat FC through multi-component,multitarget and multi-channel,but its mechanism still needs to be confirmed in vivo and in vitro.