基于网络药理学与实验探讨裘氏内异方治疗子宫内膜异位症的作用机制  

The mechanism of Qiu's Neiyi decoction in the treatment of endometriosis based on network pharmacology and experimental investigation

作　　者：李慧 杨华娣[1] 毛佩瑜 张婷[1] 陆申奕 叶恬恬 LI Hui;YANG Hua-di;MAO Peiyu;ZHANG Ting;LU Shenyi;YE Tian-tian(Department of Gynecology,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,Zhejiang 310006,China;The First Clinical College,Zhejiang University of Traditional Chinese Medicine,Hangzhou,Zhejiang 310053,China)

机构地区：[1]浙江中医药大学附属第一医院妇科,杭州310006 [2]浙江中医药大学第一临床学院,杭州310053

出　　处：《浙江中西医结合杂志》2024年第2期118-128,共11页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学青年基金项目(No.82104909);浙江省中医药科技计划项目(No.2023ZL036)。

摘　　要：目的运用网络药理学结合动物实验探究裘氏内异方治疗子宫内膜异位症(EMs)的作用机制。方法利用超高效液相色谱-飞行时间质谱(UPLC-Q/TOF-MS)联用技术结合文献检索筛选出裘氏内异方有效活性成分;于中医药系统药理学平台(TCMSP)获取活性成分的基因靶标;于基因名片数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、DisGeNET、DRUGBANK、数据库筛选疾病相关靶点,维恩分析获得药物与疾病的共同靶点;通过蛋白质相互作用(STRING11.0)数据库平台,构建蛋白互作(PPI)网络,筛选核心作用靶点;利用Cytosacpe软件构建活性成分-靶标网络;利用生物学信息注释数据库(DAVID)数据库平台分析京都基因与基因组百科全书(KEGG)通路。通过子宫异位内膜模型大鼠进行相关验证,随机数字表法分为六组,分别为正常组(假手术组)、模型组(空白对照组)、孕三烯酮组(阳性对照组)、裘氏内异方高剂量组、裘氏内异方中剂量组、裘氏内异方低剂量组,每组10只。不同药物处理4周,测定各组子宫内膜异位病灶面积及病变的粘连评分,并进行病理形态学观察。同时测定各组经网络药理学筛选出的最有可能的核心靶标和通路的靶蛋白和靶基因表达水平,以验证裘氏内异方治疗EMs的机制。结果共筛选出裘氏内异方有效活性成分19种,对应裘氏内异方的240个靶标。3816个基因与EMs密切相关,其中132个与裘氏内异方的靶点重叠,被认为与治疗相关。裘氏内异方治疗EMs的主要活性成分有木犀草苷、槲皮素、延胡索甲素、淫羊藿苷、山柰酚等,对交集靶点的PPI网络进行拓扑分析,得到丝氨酸/苏氨酸激酶1(AKT1)、白细胞介素-6(IL-6)、血管内皮生长因子A(VEGFA)、表皮生长因子受体(EGFR)、转录因子JUN等核心作用靶点,富集分析发现裘氏内异方治疗EMs的作用机制可能与PI3K-AKT、P53、雌激素等信号通路有关,其中排名第1位的Objective To explore the mechanism of Qiu's Neiyi decoction in treating endometriosis(EMs)through a combination of network pharmacology and animal experiments.Methods The active ingredients in Qiu's Neiyi decoction were identified using ultra-high performance liquid chromatography-time-of-flight mass spectrometry combined with a literature search.Gene targets of the active ingredients were obtained from the Traditional Chinese Medicine Systems Pharmacology database.Disease-related targets were screened in the DisGeNET,DRUGBANK,GeneCards,and OMIM databases.Common targets between drugs and diseases were obtained using Venn analysis.A protein interaction(PPI)network was established to screen the core targets using the STRING11.0 database.The active ingredient-target network was constructed using Cityscape software.The KEGG pathway was analyzed using the DAVID database.The rat model of endometriosis was developed and randomly divided into 6 groups using a random number table method:normal(sham operation group),model(blank control group),pregntrienone(positive control group),high dose(QNY-H group),medium dose(QNY-M group)and low dose(QNY-L group)groups(n=10 per group).After 4 weeks of treatment with different drugs,the area of endometriotic lesions,the adhesion score,and pathological morphology were assessed in each group.At the same time,the expression levels of target proteins and genes of the most likely core targets and pathways screened by network pharmacology in each group were determined to validate the mechanism of Qiu's Neiyi decoction in treating EMs.Results A total of 19 active ingredients of Qiu's Neiyi decoction were identified,corresponding to 240 targets of the decoction.Among the 3816 genes closely related to EMs,132 overlapped with targets of Qiu's Neiyi decoction,which are thought to be associated with its therapeutic effect.The main active components of Qiu's Neiyi decoction for treating EMs include luteolin,quercetin,corydaline,icariin,kaempferol,etc.Topological analysis of the PPI network of inter

关 键 词：子宫内膜异位症 网络药理学 实验验证 裘氏内异方 

分 类 号：R285[医药卫生—中药学]