基于网络药理学方法研究阿司匹林丁香酚酯防治犬心血管疾病的作用机制  

Mechanism of AEE in Preventing and Curing Canine Cardiovascular Diseases Based on Network Pharmacological Method

作　　者：焦钰婷 焦增华[1] 杨孝朴[2] 李剑勇[1] JIAO Yuting;JIAO Zenghua;YANG Xiaopu;LI Jianyong(Key Laboratory of New Animal Drug Project of Gansu Province,Key Laboratory of Veterinary Pharmaceutical Development,Ministry of Agriculture and Rural Affairs,Lanzhou Institute of Husbandry and Pharmaceutical Science of CAAS,Lanzhou 730050,China;College of Veterinary Medicine,Gansu Agricultural University,Lanzhou 730070,China)

机构地区：[1]中国农业科学院兰州畜牧与兽药研究所农业农村部兽用药物创制重点实验室甘肃省新兽药工程重点实验室,兰州730050 [2]甘肃农业大学动物医学院,兰州730070

出　　处：《中国畜牧兽医》2019年第4期1191-1198,共8页China Animal Husbandry & Veterinary Medicine

基　　金：国家自然科学基金项目(31572573);中央级事业单位基本科研业务费(1610322017016)

摘　　要：试验旨在采用网络药理学方法探讨阿司匹林和丁香酚的靶点、基因富集和通路来推测阿司匹林丁香酚酯(AEE)防治犬心血管疾病的作用机制。首先从DrugBank数据库检索阿司匹林、丁香酚获得其作用靶点,进而构建化合物-靶点网络,再将其靶点上传至STRING数据库,物种选择犬,得到作用于犬蛋白质-蛋白质相互作用(PPI)网络图,最后将作用于犬的靶点上传至DAVID数据库,物种选择犬,筛选出错误率<0.01的基因富集和KEGG通路,从而构建靶点-通路网络图,用以推测AEE防治犬心血管疾病的作用机制。通过检索分析可知,阿司匹林和丁香酚已知的相应靶点有15个,其中8个靶点可作用于犬,关键靶点涉及TP53基因、NF-κB、雄激素受体、前列腺素G/H合成酶1;基因功能富集(GO)条目4个,其中分子功能2个,涉及甾体结合和转录因子活性、序列特异性DNA结合,生物过程2个,涉及到DNA转录模板和DNA模板转录的正向调节;KEGG通路2条,涉及前列腺癌和癌症信号通路。综上所述,推测AEE可能通过调控TP53基因、NF-κB、雄激素受体、前列腺素G/H合成酶1等靶点,基因功能富集于DNA转录模板、甾体结合、转录因子活性、序列特异性DNA结合、DNA模板转录的正向调控,通过前列腺癌及其他癌症信号通路来治疗犬心血管疾病。The target,gene enrichment and pathway of aspirin and eugenol were investigated by network pharmacological method in order to speculate the action mechanism of aspirin eugenol ester(AEE)on preventing and curing canine cardiovascular diseases.From methodology,aspirin and eugenol were searched from DrugBank database to obtain their target,and then the compound-target network,the canine protein-protein interaction(PPI)network and target-pathway network were constructed.Then the targets were uploaded to the STRING database,the species was selected as canine,and the PPI network diagram was obtained.Finally,the targets acting on canine were uploaded to the DAVID database,and the species was selected as canine.Gene enrichment and KEGG pathway with false discovery rate<0.01 were screened out.These networks were used to speculate the mechanism of action of AEE on preventing and curing canine cardiovascular diseases.The results showed that there were 15 known targets related to aspirin and eugenol,of which 8 were corresponding with canine.Key targets included TP53 gene,NF-κB,androgen receptor and prostaglandin G/H synthetase 1.There were 4 gene function enrichment(GO)entries,including 2 molecular functions,involving steroid binding and transcription factor activity,sequence specific DNA binding,and 2 biological processes,involving DNA transcription template and its positive regulation.There were 2 KEGG pathways involved in prostate cancer and cancer signaling pathways.This study suggested that AEE might regulate TP53 gene,NF-κB,androgen receptor,prostaglandin G/H synthetase 1,etc.Gene functions were enriched in DNA template transcription,steroid binding,transcription factor activity and specific DNA sequence binding,and positive regulation of DNA template transcription.AEE could use prostate cancer and other cancer signaling pathways to treat canine cardiovascular disease.

关 键 词：阿司匹林丁香酚酯(AEE) 阿司匹林 丁香酚 网络药理学 

分 类 号：R285.5[医药卫生—中药学]