基于网络药理学探讨中药复方治疗奶牛子宫内膜炎的作用机制

doi:10.16431/j.cnki.1671-7236.2022.04.037

摘要/Abstract

摘要： 【目的】通过网络药理学对丹参、益母草、黄芩、连翘组成的中药复方进行分析,研究其有效成分治疗奶牛子宫内膜炎的潜在作用靶点,并对靶点作用通路的机制进行阐述。【方法】利用TCMSP数据库筛选药物成分作用靶点,通过NCBI、GeneCard、geneMap、TTD、DrugBank查找奶牛子宫内膜炎的相关靶点,筛选出药物成分靶点与奶牛子宫内膜炎相关靶点的共有基因靶点,作为该中药复方治疗奶牛子宫内膜炎的预测靶点,并上传到STRING数据库建立蛋白互作(PPI)网络,通过Cytoscape 3.8.2软件根据连接度对PPI网络进行筛选,找到其核心靶点。运用Metascape数据库对核心靶点进行GO功能与KEGG通路富集分析。【结果】从该中药复方中筛出有效活性成分133种,主要包括槲皮素、山奈酚、黄芩素、丹参酮ⅡA等,通过药物成分找到对应靶点蛋白292个,通过数据库找到奶牛子宫内膜炎的相关靶点130个,筛出中药复方治疗奶牛子宫内膜炎的预测靶点24个,其中核心靶点7个,包括肿瘤坏死因子、蛋白激酶、前列腺素内过氧化物合酶2等。GO功能富集分析得到生物过程20个条目、分子功能6个条目及细胞组分6个条目,生物过程包括脂多糖的反应、白细胞-细胞黏附的正向调节、对无机物的反应等;分子功能包括信号受体活性调节、转录辅激活子的结合、血红素结合等;细胞组分包括细胞膜筏、薄膜侧面、颗粒分泌腔等。KEGG通路富集分析涉及20个基因,参与调控的通路有9条,其中涉及基因较多的包括AGE-RAGE信号通路、癌症蛋白聚糖通路、血流剪切应力与动脉粥样硬化通路及Th17细胞分化通路。【结论】该中药复方可能是通过调控肿瘤坏死因子、蛋白激酶、前列腺素内过氧化物合酶2等靶点,通过参与AGE-RAGE信号通路及Th17细胞的分化对奶牛子宫内膜炎产生治疗作用。

关键词: 中药复方; 网络药理学; 奶牛; 子宫内膜炎; 作用机制

Abstract: 【Objective】 The traditional Chinese medicine compound consisting of Salvia miltiorrhiza,Leonurus heterophyllus, Scutellaria baicalensis and Forsythia suspensa was analyzed by network pharmacology,in order to study the possible targets of its effective components for treating dairy cow endometritis,and explain the mechanism of target action pathway.【Method】 TCMSP database was used to screen the target of drug components,NCBI,GeneCard,geneMap,TTD and DrugBank were used to find the related targets of cow endometritis,and the common gene targets of drug components and cow endometritis were screened out,which were used as the predicted targets for the treatment of cow endometritis with this traditional Chinese medicine compound,and then uploaded to STRING database to establish PPI network,which was screened by Cytoscape 3.8.2 software according to the connectivity.Metascape database was used to analyze the enrichment of GO function and KEGG pathway of core targets,and its mechanism was explored.【Result】 133 kinds of effective active ingredients were screened out from the traditional Chinese medicine compound,mainly including quercetin,kaempferol,baicalein,tanshinone ⅡA,etc.,292 corresponding target proteins were found through drug ingredients,130 related targets of cow endometritis were found through database,and 24 predicted targets of traditional Chinese medicine compound for treating cow endometritis were screened out,among which 7 core targets were screened out,including tumor necrosis factor,protein kinase and prostaglandin-endoperoxide synthase 2.GO function enrichment analysis resulted in 20 items of biological process,6 items of molecular function and 6 items of cell component.Biological processes included the reaction of lipopolysaccharide,the positive regulation of leukocyte-cell adhesion,the reaction to inorganic substances,etc.Molecular function included signal receptor activity regulation,transcription coactivator binding,heme binding and so on.Cell components included cell membrane raft,membrane side,granular secretory cavity,etc.The enrichment analysis of KEGG pathway involved 20 genes,and there were 9 pathways involved in regulation.Among them,many genes included AGE-RAGE signaling pathway,cancer proteoglycan pathway,blood flow shear stress and atherosclerosis pathway and Th17 cell differentiation pathway.【Conclusion】 The traditional Chinese medicine compound might have therapeutic effect on cow endometritis by regulating tumor necrosis factor,protein kinase,prostaglandin-endoperoxide synthase 2 and other targets,and by participating in AGE-RAGE signaling pathway and Th17 cell differentiation.

Key words: traditional Chinese medicine compound; network pharmacology; dairy cow; endometritis; action mechanism

中图分类号:

S853.7

王钺夫, 徐闯, 崔一喆. 基于网络药理学探讨中药复方治疗奶牛子宫内膜炎的作用机制[J]. 中国畜牧兽医, 2022, 49(4): 1545-1555.

WANG Yuefu, XU Chuang, CUI Yizhe. Study on the Mechanism of Traditional Chinese Medicine Compound in the Treatment of Endometritis in Dairy Cows Based on Network Pharmacology[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(4): 1545-1555.

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