基于网络药理学与分子对接技术探讨补肾活血方治疗反复种植失败的作用机制  

Study on the mechanism of Bu-Shen-Huo-Xue Recipe in the treatment of recurrent implantation failure based on network pharmacology and bioinformatics

作　　者：夏利显 叶倩 邹莉 崔英 Xia Lixian;Ye Qian;Zou Li;Cui Ying(Fuwai Hospital,National Cardiovascular Center,Chinese Academy of Medical Sciences,Health Department,Beijing 100037,China;Jiangxi University of Traditional Chinese Medicine,Graduate School,Jiangxi,Nanchang 330004,China;Jiangxi Provincial Maternal and Child Health Hospital,TCM department,Jiangxi Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Female Reproduction,Jiangxi,Nanchang 330006,China)

机构地区：[1]中国医学科学院国家心血管中心阜外医院保健科,北京100037 [2]江西中医药大学研究生院,江西南昌330004 [3]江西省妇幼保健院中医科江西省中西医结合女性生殖重点研究室,江西南昌330006

出　　处：《发育医学电子杂志》2021年第3期206-213,共8页Journal of Developmental Medicine (Electronic Version)

基　　金：江西省重点研发计划项目(20171BBG70118)。

摘　　要：目的联合运用网络药理学与分子对接方法分析补肾活血方治疗反复种植失败(recurrent implantation failure,RIF)的作用机制。方法检索数据库TCMSP和BATMAN-TCM得到补肾活血方的药物活性成分及作用靶标;检索GEO数据库获得差异基因;检索GeneCards数据库获得RIF相关的已知靶基因。整合补肾活血方作用靶标与两数据库获得的基因得到交集靶蛋白。运用Cytoscape 3.7.2软件绘制“补肾活血方-活性成分-交集靶蛋白-RIF”网络图;利用STRING在线平台构建交集靶蛋白互作关系的PPI(protein-protein interaction);使用Metascape数据库对交集靶蛋白进行GO和KEGG分析;最后利用PyMoL、AuTo Dock软件对关键靶点和活性成分间的相互作用进行分子对接验证。结果补肾活血方检索出277个靶标,GEO2R获得显著差异基因390个,RIF相关靶标3454个,将药物靶标与疾病靶标相映射得到交集靶蛋白11个。GO分析显示交集靶蛋白主要涉及多细胞生物稳态、内皮细胞迁移、脂质生物合成过程、水解酶活性正调控、上皮细胞迁移、平滑肌收缩、组织迁移等生物过程;小窝、膜筏、膜微域、膜区、质膜筏等细胞组成;氧化还原酶活性、血红素结合、四吡咯结合、辅因子结合、蛋白质同源二聚活性等分子功能;KEGG信号通路主要富集在癌症途径、化学致癌、药物代谢、钙信号途径等。槲皮素、山奈酚、木犀草素等为补肾活血方的主要活性成分,前列腺素内氧化酶还原酶2(prostaglandinendoperoxide synthase 2,PTGS2)、雌激素受体1(estrogen receptor 1,ESR1)、细胞色素P4503A4酶(cytochrome P4503A4,CYP3A4)、5-羟色胺2A受体(5-hydroxytryptamine receptor 2A,HTR2A)等为其主要作用靶标。分子对接显示槲皮素、山奈酚、木犀草素均能与PTGS2、ESR1、CYP3A4、HTR2A稳定的结合。结论补肾活血方中槲皮素、山奈酚、木犀草素等多种活性化合物可能通过作用于PTGS2、ESR1、CYP3A4、HTR2A�Objective Network pharmacology and bioinformatics were used to analyze the molecular mechanism of Bu-Shen-Huo-Xue Recipe(BSHXR)in the treatment of recurrent implantation failure(RIF).Methods The database TCMSP and BATMAN-TCM were retrieved,and the active components and targets of BSHXR were obtained.Differential genes were obtained by using GEO database.The known target genes related to RIF were obtained by searching GeneCards database.The action targets of BSHXR and the two database genes were intergrated for common genes.Meanwhile,Cytoscape 3.7.2 software was used to construct the common gene network map,and the network diagram was constructed based on herbcomponent-target-pathway.Finally,the DAVID database was used for GO and KEGG analysis of common genes.Results A total of 277 targets were retrieved from BSHXR.GEO2R obtained 390 significantly different genes.from GEO2R.There are 3454 RIF-related targets.The mapping of drug target and disease target resulted in 11 common genes.GO analysis showed that the intersection target proteins were mainly involved in multi-cellular homeostasis,endothelial cell migration,lipid biosynthesis,positive regulation of hydrolase activity,epithelial cell migration,smooth muscle contraction,tissue migration and other biological processes;cell composition of fossa,membrane raft,membrane microdomain,membrane region,plasma membrane raft,etc;molecular functions such as oxidoreductase activity,heme binding,tetrapyrrole binding,cofactor binding,protein homodimerization activity,etc.KEGG signaling pathway was mainly enriched in cancer pathway,chemical carcinogenesis,drug metabolism,calcium signaling pathway,etc.Quercetin,kaundol and luteolin were the main active components of BSHXF,and prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor 1(ESR1),cytochrome P4503A4(CYP3A4),5-hydroxytryptamine receptor 2A(HTR2A)were the main targets of action.Molecular docking showed that quercetin,kaolferol and luteolin could stably bind to PTGS2,ESR1,CYP3A4 and HTR2A.Conclusions A variety of ac

关 键 词：反复种植失败 补肾活血方 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]