基于生物信息学和动物实验探讨完带汤治疗盆腔炎性疾病后遗症的作用机制  

Mechanism of Wandai Decoction in Treating Sequelae of Pelvic Inflammatory Disease Based on Bioinformatics and Animal Experiments

作　　者：龙茜 朱肄懿 孔小娟 林洁[2] LONG Xi;ZHU Yiyi;KONG Xiaojuan;LIN Jie(Hunan University of Chinese Medicine,Changsha Hunan China 410208;The First Hospital of Hunan University of Chinese Medicine,Changsha Hunan China 410007)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南中医药大学第一附属医院,湖南长沙410007

出　　处：《中医学报》2024年第7期1519-1526,共8页Acta Chinese Medicine

基　　金：湖南省卫生健康委员会课题项目(202205014138);湖南中医药大学校级科研基金项目(ZYYDX201753)。

摘　　要：目的:基于生物信息学、分子对接及动物实验探讨完带汤治疗盆腔炎性疾病后遗症(sequelae of pelvic inflammatory disease,SPID)的作用机制。方法:通过基因表达综合(Gene Expression Omnibus,GEO)数据库检索SPID相关数据集,借助limma分析筛选差异表达基因。通过HERB数据库检索完带汤作用靶点,将其与SPID差异表达基因取交集,作为完带汤治疗SPID的关键靶点。将关键靶点导入STRING数据库,绘制蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图。通过Cytoscape软件的Analyze Network插件进行拓扑分析,从而筛选核心靶点。通过Web Gestalt数据库进行基因本体(Gene Ontology,GO)功能分析,借助Reactome平台进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。采用HERB数据库和中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取核心靶点对应的化学成分,将其作为完带汤治疗SPID的关键成分。利用AutoDock软件对完带汤关键成分与核心靶点进行分子对接验证。从46只SD大鼠中随机选取10只作为空白组,其余大鼠沿输卵管-卵巢方向注入混合菌液0.1 mL从而建立SPID模型。将造模成功的大鼠随机分为模型组、头孢呋辛酯组、完带汤组,每组7只,灌胃21 d,每日1次。HE染色观察输卵管病理形态学改变,ELISA检测血清转化生长因子-β1(transforming growth factor-β1,TGF-β1)水平。结果:从GEO数据库获取GSE165004数据集,筛选得到SPID的差异表达基因3073个。完带汤作用靶点446个,完带汤治疗SPID的关键靶点58个。通过PPI网络筛选得到10个核心靶点,包括丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、糖原合成酶激酶-3β(glycogen synthase kinase-3 beta,GSK-3β)、半胱氨酸天冬氨酸蛋白酶9(caspase 9,CASP9)等。GO和KEGG分析结果主要涉及白细胞介素-4和白细胞介素Objective:To Explore the mechanism of Wandai Decoction in treating sequelae of pelvic inflammatory disease(SPID)based on bioinformatics,molecular docking and animal experiments.Methods:Retrieve SPID related datasets from the Gene Expression Omnibus(GEO)database,and screen differentially expressed genes using limma analysis.Retrieve the target of Wandai Decoction through the HERB database and intersect it with the differentially expressed genes of SPID as the key target of Wandai Decoction for treating SPID.Import key targets into the STRING database and draw a protein-protein interaction(PPI)network diagram.Perform Gene Ontology(GO)functional analysis using the WebGestalt database,and conduct Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis using the Reactome platform.Use AutoDock software to perform molecular docking validation on the active ingredients and key targets of Wandai Decoction.Ten SD rats were randomly selected from 46 as the blank group,while the remaining rats were injected with 0.1 mL of mixed bacterial solution into fallopian tube to ovary direction to establish a SPID model.The successfully modeled rats were randomly divided into model group,cefuroxime axetil group and Wandai Decoction group,with 7 rats in each group.They were orally administered for 21 days,once a day.Observe pathological and morphological changes in the oviduct with HE staining,and ELISA is used to detect serum transforming growth factor-β1(TGF-β1)levels.Results:The GSE165004 dataset was obtained from the GEO database,and 3073 differentially expressed genes of SPID were screened.There are 446 targets of action for Wandai Decoction,and 58 key targets for treating SPID with Wandai Decoction.10 core targets were identified through PPI network screening,including mitogen-activated protein kinase 1(MAPK1),glycogen synthase kinase-3β(GSK-3β),caspase-9(CASP9),etc.The GO and KEGG analysis results mainly involve the signals of interleukin-4 and interleukin-13,the intrinsic pathways of apoptosis,biological regulation,me

关 键 词：完带汤 盆腔炎性疾病后遗症 生物信息学 动物实验 TGF-Β1 毛蕊异黄酮 大鼠 

分 类 号：R285[医药卫生—中药学]