基于网络药理学的乌锦颗粒治疗羔羊痢疾的作用机制研究

doi:10.16431/j.cnki.1671-7236.2021.07.036

摘要/Abstract

摘要： 试验旨在通过网络药理学的挖掘功能对乌锦颗粒治疗羔羊痢疾的有效成分进行筛选，并对其潜在作用靶点和可能的通路进行阐释。依据中药系统药理学数据库与分析平台（TCMSP）解析乌锦颗粒各单味药的主要有效化合物，同时查找其所对应的靶点，没有靶点的化合物再次通过Swiss Target Prediction数据库对其靶点进行预测，最后得到有事实靶点的化合物及其对应靶点蛋白，采用Cytoscape 3.7.1软件构建有效成分-靶点蛋白网络图；将筛选出的靶点蛋白上传至String在线数据库，构建乌锦颗粒作用于羔羊（Ovis aries）痢疾的蛋白质-蛋白质相互作用（PPI）图，最后将PPI网络中的核心靶点上传至DAVID数据库进行GO功能和KEGG通路富集分析，同时进行基因功能聚类分析。结果显示，共筛选出有事实靶点的化合物22种，包括山奈酚、豆甾醇、花生四烯酸甲酯、槲皮素及鞣花酸等，化合物对应靶点蛋白去重后共计129个；PPI网络图显示节点数为74，边数为287，平均节点度为7.76，核心靶点蛋白共计67个，包括INSR、NR3C1、ESR1、PLG及PGR等；GO功能富集分析得到与生物过程（BP）相关的条目54个（FDR<0.05），与细胞成分（CC）相关的条目11个（FDR<0.05），与分子功能（MF）相关的条目22个（FDR<0.05），GO功能富集基因计数较多的条目有转录（transcription）、质膜（plasma membrane）及锌离子结合（zinc ion binding）等；KEGG通路富集结果涉及50个基因，基因协同参与的调控通路43条，涉及基因较多的有神经活性配体-受体相互作用（neuroactive ligand-receptor interaction）、癌症的途径（pathways in cancer）及补体和凝血级联（complement and coagulation cascades）等；基因功能分类结果显示，64个核心靶基因中有12个基因具有聚类结果，将其分为功能不同的2组，分别为聚类1组（富集分数6.11，涉及7个核心靶基因）和聚类2组（富集分数2.84，涉及5个核心靶基因）。综上，乌锦颗粒可能是通过多种化合物作用于多种不同的靶点，参与多种通路的调节来实现对羔羊痢疾的治疗机制。

关键词: 网络药理学; 乌锦颗粒; 羔羊痢疾; 靶点; 作用机制

Abstract: The purpose of the experiment was to screen the effective ingredients of Wujin granules in the treatment of lamb dysentery through the mining function of network pharmacology,and explain its potential targets and possible pathways.According to the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP),the main effective compounds of each single medicine of Wujin granules were analyzed,and at the same time their corresponding targets were searched.Compounds without targets were analyzed again by the Swiss Target Prediction database for their targets,it was predicted that the compound with factual target and its corresponding target protein were finally obtained.Cytoscape 3.7.1 software was used to construct the network diagram of the effective ingredient-target protein,the selected target protein was uploaded to the String online database to construct Wujin granules acting on the protein-protein interaction (PPI) map of lamb (Ovis aries) dysentery,and finally uploaded the core targets in the PPI network to the DAVID database for GO function and KEGG pathway enrichment analysis,and at the same time performed gene function cluster analysis.The results showed that a total of 22 compounds with de facto targets were screened,including kaempferol,stigmasterol,methyl arachidonic acid,quercetin,ellagic acid,and so on,and a total of 129 compounds corresponding to target proteins were deduplicated.The PPI network diagram showed that the number of nodes was 74,the number of edges was 287,the average node degree was 7.76,and a total of 67 core target proteins,including INSR,NR3C1,ESR1,PLG,PGR,and so on.GO function enrichment analysis showed that 54 items were related to biological process (BP) (FDR<0.05),11 items were related to cell component (CC) (FDR<0.05),22 items were related to molecular function (MF) (FDR<0.05).GO function enrichment gene items with more count included transcription,plasma membrane,zinc ion binding,and so on,KEGG pathway enrichment results involved 50 genes,and 43 regulatory pathways involved in gene coordination,neuroactive ligand-receptor interaction,pathways in cancer,complement and coagulation cascades,and so on,involved more genes.Gene function classification results showed that of 64 cores among the target genes,12 genes had clustering results.They were divided into two groups with different functions,namely group 1 (enrichment score 6.11,involving 7 core target genes) and group 2 (enrichment score 2.84,involving 5 core target genes).In conclusion,Wujin granules might act on a variety of different targets through a variety of compounds,and participate in the regulation of multiple pathways to achieve the therapeutic mechanism of lamb dysentery.

Key words: network pharmacology; Wujin granules; lamb dysentery; target; mechanism of action

中图分类号:

S853.74

蒋威, 武小虎, 杨洁, 丁学智, 李宏胜, 沈文祥, 王东升, 王胜义, 严作廷. 基于网络药理学的乌锦颗粒治疗羔羊痢疾的作用机制研究[J]. 中国畜牧兽医, 2021, 48(7): 2594-2606.

JIANG Wei, WU Xiaohu, YANG Jie, DING Xuezhi, LI Hongsheng, SHEN Wenxiang, WANG Dongsheng, WANG Shengyi, YAN Zuoting. Study on the Mechanism of Action of Wujin Granules in Treating Lamb Dysentery Based on Network Pharmacology[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(7): 2594-2606.

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