基于网络药理学和动物实验探讨芍胡调经方治疗原发性痛经的作用机制  

Action Mechanism of Shaohu Tiaojing Formula in Treatment of Primary Dysmenorrhea Based on Network Pharmacology and Animal Experiments

作　　者：段佩利[1,2] 院军 赵萌 张振凌 DUAN Peili;YUAN Jun;ZHAO Meng;ZHANG Zhenling(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou Henan China 450046;The Third Affiliated Hospital to Henan University of Chinese Medicine,Zhengzhou Henan China 450008)

机构地区：[1]河南中医药大学药学院,河南郑州450046 [2]河南中医药大学第三附属医院,河南郑州450008

出　　处：《中医学报》2024年第9期1974-1982,共9页Acta Chinese Medicine

基　　金：张磊国医大师传承工作室项目[人社部发(2017)45号]。

摘　　要：目的:基于网络药理学和分子对接分析芍胡调经方治疗原发性痛经(primary dysmenorrhea,PD)的作用机制,并通过动物实验加以验证。方法:采用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)和PharmMapper数据库分析芍胡调经方的活性成分与靶点,在GeneCards数据库和DrugBank数据库搜索痛经的靶点,并获取两者的交集靶点。通过Cytoscape 3.9.1软件构建“活性成分-交集靶点”网络,根据拓扑分析筛选关键成分。将交集靶点导入STRING数据库,构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,采用Network Analysis插件进行拓扑分析,从而筛选核心靶点。借助Metascape网站进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析,最后进行分子对接验证。40只SD大鼠随机分为空白组、模型组、芍胡调经方组、布洛芬组,每组10只。除空白组外,其余大鼠采用冰水浴联合苯甲酸雌二醇皮下注射以及缩宫素腹腔注射法建立PD模型。造模第3天开始给药,连续12 d。末次给药后,计算大鼠的扭体潜伏期和扭体次数;HE染色观察子宫病理形态,ELISA法检测血清雌二醇(estradial,E2)和前列腺素E2(prostaglandin E2,PGE2)含量。结果:芍胡调经方活性成分210个,靶点255个。痛经靶点831个,其与芍胡调经方的交集靶点67个,包括信号转导和转录激活因子3(signal transducer and activator of transduction 3,STAT3)、蛋白激酶B(protein kinase B,AKT1)、肿瘤坏死因子(tumor necrosis factor,TNF)等。槲皮素、山柰酚、β-谷甾醇、木犀草素、柚皮素、芍药苷和甘草苷可能是芍胡调经方治疗痛经的关键成分。STAT3、AKT1、TNF、肿瘤蛋白p53(tumor protein p53,TP53)、雌激素受体1(estrogen receptor 1,ESR1)、白细胞介素-6(interleukin-6,IL-6)可能是芍胡调经方治疗痛经的核心靶点。KEGG通路主要包括PI3K-Akt�Objective:To analyze the mechanism of action of Shaohu Jiaojing Formula in the treatment of primary dysmenorrhea(PD)by network pharmacology and molecular docking,and to verify it through animal experiments.Methods:The active ingredients and targets of Paeonia Hu Pharmacology Formula were analyzed by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and PharmMapper database,and the targets of dysmenorrhea were searched in GeneCards database and DrugBank database.and obtain the intersection target of the two.Cytoscape 3.9.1 software was used to construct an"active ingredient-intersection target"network to screen key components based on topological analysis.The intersecting targets were imported into the STRING database to construct a protein-protein interaction(PPI)network,and the Network Analysis plug-in was used for topological analysis to screen the core targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)was analyzed with the help of the Metascape website,and finally the molecular docking verification was carried out.Forty SD rats were randomly divided into blank group,model group,Shaohu Tiaojing Formula group,and ibuprofen group,with 10 rats in each group.Except for the blank group,the PD model was established by ice water bath combined with subcutaneous injection of estradiol benzoate and intraperitoneal injection of oxytocin.The drug was administered on the 3rd day of modeling for 14 consecutive days.After the last dose,the writhing latency and the number of writhing times in the rats were calculated.The pathological morphology of the uterus was observed by HE staining,and the serum estradial(E2)and prostaglandin 2(PGE2)levels were detected by ELISA.Results:There were 210 active ingredients and 255 targets of Shaohu Jiaojing Formula.There were 831 dysmenorrhea targets,and 67 intersecting targets with Paeonia chinensis,including signal transducer and activator of transduction 3(STAT3),protein kinase B(AKT1),tumor necrosis factor(TNF),etc.Quercetin,kaempferol

关 键 词：芍胡调经方 原发性痛经 网络药理学 PGE2 E2 大鼠 张磊 国医大师 

分 类 号：R285.5[医药卫生—中药学]