基于网络药理学与分子对接探讨二至丸“异病同治”治疗围绝经期综合征及异常子宫出血的作用机制  

Exploring the mechanism of action of Er Zhi pill in the treatment of perimenopausal syndrome and abnormal uterine bleeding based on network pharmacology and molecular docking

作　　者：伍娟娟[1] 韦美秀 刘锐[2] WU Juanjuan;WEI Meixiu;LIU Rui(Department of Gynecology,Ruikang Hospital Affilicatecl to Guangxi University of Chinese Medicine,Nanning 530011,China)

机构地区：[1]广西中医药大学附属瑞康医院妇科,南宁530011 [2]广西中医药大学附属瑞康医院老年病科,南宁530011 [3]广西中医药大学研究生院

出　　处：《环球中医药》2023年第7期1340-1348,共9页Global Traditional Chinese Medicine

基　　金：广西壮族自治区中医药局2020年自筹经费科研课题(GZZC2020109);广西中医药大学2019年博士科研启动基金项目(2019BS039)。

摘　　要：目的通过网络药理学与分子对接技术探讨二至丸“异病同治”治疗围绝经综合征和异常子宫出血的作用机制。方法利用TCMSP数据库获取二至丸的药物活性成分及作用靶点,通过Genecard数据库获取围绝经综合征和异常子宫出血疾病相关靶点;获取药物活性成分作用靶点与疾病相关靶点的交集靶点(共有靶点),即二至丸异病同治治疗围绝经期综合征及异常子宫出血的潜在作用靶点;利用Cytoscape 3.9.0构建药物-活性成分-靶点网络,并筛选出核心活性成分,运用STRING数据库构建共有靶点蛋白互作(protein-protein interaction,PPI)网络,筛选核心靶点;通过Metascape数据库对共有靶点进行GO及KEEG富集分析。利用AutoDock4.2.6对核心靶点及活性成分进行分子对接。结果获得二至丸药物活性成分23种,二至丸异病同治围绝经综合征和异常子宫出血潜在作用靶点28个;槲皮素、木犀草素、山奈酚等被确定为关键活性成分,表皮生长因子受体(epithelial growth factor receptor,EGFR)、雌激素受体1(estrogen receptor 1,ESR1)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、白细胞介素1β(interleukin-1 beta,IL-1β)、缺氧诱导因子-1α(hypoxia-inducible factor 1-alpha,HIF-1α)等被确定为核心靶点。KEGG通路富集分析得到96条相关通路,与AGE-RAGE、PI3K-Akt、MAPK、HIF-1等信号通路密切相关。分子对接显示关键靶点与关键活性成分有良好的潜在结合力。结论二至丸治疗围绝经期综合征及异常子宫出血涉及多种成分、多个靶点及多条信号通路,可能通过抗氧化、抗炎、抑制颗粒细胞凋亡、调节激素水平、促进卵泡发育等作用,改善卵巢功能,发挥“异病同治”作用。Objective To investigate the mechanism of action of Er Zhi pill in the treatment of perimenopausal syndrome and abnormal uterine bleeding by using network pharmacology and molecular docking techniques.Methods To obtain the active ingredients and targets of Er Zhi pill using TCMSP database,and to obtain the disease-related targets of perimenopausal syndrome and abnormal uterine bleeding using Genecard database;to obtain the intersection targets(common targets)between the active ingredients and disease-related targets,i.e.,the potential targets of Er Zhi Pill for heteropathic treatment of perimenopausal syndrome and abnormal uterine bleeding;to construct the drug-active ingredient-target using Cytoscape 3.9.0 was used to construct the drug-active ingredient-target network and screen out the core active ingredients,and the STRING database was used to construct the shared target protein interaction(PPI)network and screen out the core targets;GO and KEEG enrichment analysis of the shared targets were performed by Metascape database.Molecular docking of the core targets and active ingredients was performed using AutoDock 4.2.6.Results 23 active ingredients of Er Zhi pill were obtained,28 potential targets of Er Zhi pill for the treatment of perimenopausal syndrome and abnormal uterine bleeding;quercetin,lignocaine and kaempferol were identified as key active ingredients,and EGFR,ESR1,VEGFA,IL-1βand HIF-1αwere identified as core targets.96 related pathways were obtained by KEGG pathway enrichment analysis,which were associated with AGE-RAGE,PI3K--Akt,MAPK,HIF-1 and other signaling pathways were closely related.Molecular docking showed good potential binding of key targets to key active ingredients.Conclusion The treatment of perimenopausal syndrome and abnormal uterine bleeding with Er Zhi pill involves multiple components,multiple targets and multiple signaling pathways,which may improve ovarian function through antioxidant,anti-inflammatory,inhibiting granulosa cell apoptosis,regulating hormone levels and promoting

关 键 词：围绝经期综合征 异常子宫出血 二至丸 异病同治 网络药理学 分子对接 

分 类 号：R255.9[医药卫生—中医内科学]