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江益娟,谢海燕.基于网络药理学的逍遥丸治疗高泌乳素血症潜在作用机制研究[J].浙江中西医结合杂志,2021,31(10):
基于网络药理学的逍遥丸治疗高泌乳素血症潜在作用机制研究
投稿时间:2021-04-08  修订日期:2021-07-09
DOI:
中文关键词:  逍遥丸  高泌素血症  网络药理学  作用机制  基因富集分析
英文关键词:XiaoyaoWan  HPRL  Network pharmacology  Mechanism of action  Gene enrichment analysis
基金项目:三种干预方法对抗精神病药物所致的高泌乳素血症的影响研究,创新研究群体科学基金
作者单位E-mail
江益娟* 浙江省衢州市第三医院 衢州 324000 jiangyij1@163.com 
谢海燕 浙江省衢州市第三医院临床药学室 衢州 324000  
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中文摘要:
      目的 研究逍遥丸治疗高泌乳素血症的潜在作用机制,为高泌乳素血症的治疗提供新的方向与靶点。方法 利用中药系统网络药理学数据库和分析平台(TCMSP)筛选出柴胡、当归、白芍、白术、茯苓、甘草与薄荷的活性成分和相关靶点;通过检索治疗靶点数据库(GeneCards、Omim和PharmGK)获取与高泌乳素血症的基因靶点,采用Cytoscape软件构建药物-活性成分-靶点-疾病网络;用STRING系统进行PPI网络分析;通过DAVID数据库进行基因功能(GO)以及用R软件进行通路注释(KEGG)富集分析。结果 从逍遥丸中共获得活性成分156个,潜在靶点116个;收集与高泌乳素血症相关的靶点14个;通过STRING系统制得PPI网络分析图;基因功能(GO)和通路注释(KEGG)富集分析结果显示,逍遥丸治疗高泌乳素血症的靶点主要富集对基因表达的正调控、信号转导、MAPK级联的正调控、RNA聚合酶II启动子的转录、应对缺氧、雌二醇刺激的细胞反应、对雌激素的反应等31个生物过程;基底外侧质膜、细胞外间隙、细胞外区域3个细胞组成;ATP酶结合、类固醇活性与结合、酶结合、蛋白结合、乙酰胆碱结合、转录激活因子活性,RNA聚合酶II启动的特异性DNA结合等13个分子功能;其靶点通路主要富集在EGFR酪氨酸激酶抑制剂耐药、癌症中的蛋白多糖、HIF-1信号通路、雌激素信号途径、乳腺癌、膀胱癌6条通路。结论 本研究采用网络药理学方法揭示了逍遥丸治疗高泌乳素血症的潜在机制,为进一步研究逍遥丸治疗高泌乳素血症的药效物质基础及作用靶点提供参考。
英文摘要:
      ABSTRACT: OBJECTIVE To study the potential mechanism of XiaoyaoWan in the treatment of HPRL and provide a new direction and target for the treatment of HPRL. METHODS The active components and related targets of Radix Bupleuri, Angelica sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis, Poria cocos, Glycyrrhiza and Mentha were screened out by TCMSP; GeneCards,OMIM and PharmGKdatabase were used to obtain gene targets of HPRL;Cytoscape software was used to construct drug-active ingredient-target-disease network; PPI network was analyzed by STRING system; Gene function (GO) analysis was carried out by David database, and path annotation (KEGG) enrichment analysis was performed by R software. RESULTS 156 active components and 116 potential targets were obtained from XiaoyaoWan;14 targets related to HPRL were collected; PPI network analysis map was made by STING system; gene function (go) and pathway annotation (KEGG) enrichment analysis results showed that the main targets of XiaoyaoWan for HPRL treatment were mainly concentrated in 31 biological processes such as positive regulation of gene expression,signal transduction, MAPK cascade, RNA polymerase II promoter transcription, cell response to hypoxia, estradiol stimulationa and response to estrogen; Basolateral plasma membrane, extracellular space and extracellular region were composed of 3 cells; 13 molecular functions including ATPase binding, steroid activity and binding, enzyme binding, protein binding, acetylcholine binding, transcriptional activator activity and specific DNA binding initiated by RNA polymerase II. The target pathway is mainly enriched in 6 pathways including EGFR tyrosine kinase inhibitor resistance, cancer proteoglycan, HIF-1 signaling pathway, estrogen signaling pathway, breast cancer, bladder cancer. CONCLUSION Based on the network pharmacological method, this study reveals the potential mechanism of XiaoyaoWan in the treatment of HPRL.
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