基于“药物-靶点-分子对接-疾病”关联网络研究五子养脏汤治疗卵巢储备功能减退的作用机制  

Study on the mechanisms of Wuzi Yangzang Decoction in the treatment of diminished ovarian reserve based on the network of"drug-target-molecule-docking-disease"associations

作　　者：沈洁 邓树梅 吴小娟 罗心如 孙铭瑶 顾一凡 苏广恒 吴媛媛[3] 罗志娟[3] SHEN Jie;DENG Shumei;WU Xiaojuan;LUO Xinru;SUN Mingyao;GU Yifan;SU Guangheng;WU Yuanyuan;LUO Zhijuan(Faculty of Chinese Medicine Science,Guangxi University of Chinese Medicine,Guangxi,Nanning 530222,China;Graduate School of Guangxi University of Chinese Medicine,Guangxi,Nanning 530222,China;Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Guangxi,Nanning 530222,China)

机构地区：[1]广西中医药大学赛恩斯新医药学院,广西南宁530222 [2]广西中医药大学研究生院,广西南宁530222 [3]广西中医药大学附属瑞康医院,广西南宁530222

出　　处：《中国医药科学》2025年第7期13-18,共6页China Medicine And Pharmacy

基　　金：广西中医药大学赛恩斯新医药学院大学生创新创业训练计划项目(S202313643031)。

摘　　要：目的基于网络药理学和分子对接探讨五子养脏汤在治疗卵巢储备功能减退中的相关分子机制。方法运用中药系统药理学数据库与分析平台(TCMSP)对五子养脏汤中的活性成分及作用靶点进行检索,并构建药物-成分-靶点网络图;通过人类基因综合数据库(GeneCards)等数据库获取卵巢储备功能减退的相关靶标,绘制药物疾病交集基因VENNY图,将数据导入STRING数据库得到蛋白质-蛋白质相互作用(PPI)网络并获取核心基因;在DAVID数据平台进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析;采用Cytoscape构建疾病-通路-靶点-成分-药物网络图;运用AutoDockTools对相关活性成分与核心靶点进行分子对接。结果通过筛选得出的53个化合物和254个药物相应靶点,建立PPI核心网络,关键蛋白涉及蛋白激酶B1(AKT1)、白蛋白(ALB)、肿瘤坏死因子(TNF)、白细胞介素(IL)1B、肿瘤蛋白53(TP53)等。GO功能富集分析取得850个条目(P<0.05),其中生物过程658个,细胞组成84个,分子功能108个;KEGG通路富集取得与卵巢储备功能低下相关(P<0.05)的143条通路,涉及癌症、液体切应力与动脉粥样硬化、晚期糖基化终末产物-受体相互作用信号通路等途径。进行分子对接后所得结果表明,五子养脏汤中的主要活性成分与核心靶点ALB、TNF等具有较好的结合活性。结论五子养脏汤中的活性化合物可通过多通路、多靶点的方式从细胞的增殖和凋亡的角度对卵巢储备功能减退进行治疗。Objective To investigate the molecular mechanism of Wuzi Yangzang Decoction in the treatment of diminished ovarian reserve based on network pharmacology and molecular docking.Methods Utilize the traditional Chinese medicine system pharmacology database and analysis platform(TCMSP)to search for the active ingredients and target points of Wuzi Yangzang Decoction,and cons truct a drug-component-target network diagram.Retrieve relevant targets for diminished ovarian reserve through databases such as the Human Gene Comprehensive Database(GeneCards),and create a VENNY diagram of drug-disease intersecting genes.Import the data into the STRING database to obtain a protein-protein interaction(PPI)network and identify core genes.Conduct gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis on the DAVID data platform.Use Cytoscape to construct a disease-pathway-target-component-drug network diagram.Perform molecular docking of relevant active ingredients and core targets using AutoDockTools.Results Through screening,53 compounds and 254 corresponding drug targets were identified,leading to the construction of a PPI core network.Key proteins included protein kinase B1(AKT1),albumin(ALB),tumor necrosis factor(TNF),interleukin(IL)-1B,and tumor protein p53(TP53).GO functional enrichment analysis yielded 850 significant entries(P<0.05),including 658 biological processes,84 cellular components,and 108 molecular functions.KEGG pathway enrichment identified 143 pathways significantly associated with diminished ovarian reserve(P<0.05),involving cancer,fluid shear stress and atherosclerosis,AGE-RAGE signaling pathway,and others.Molecular docking results demonstrated that the main active components of Wuzi Yangzang Decoction exhibited strong binding affinity with core targets such as ALB and TNF.Conclusion The active compounds in Wuzi Yangzang Decoction can be used to treat diminished ovarian reserve from the perspective of cell proliferation and apoptos is in a m ulti-pathway and multi-target approach.

关 键 词：卵巢储备功能减退 五子养脏汤 网络药理学 分子对接 作用机制 

分 类 号：R271.9[医药卫生—中西医结合]