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目的探讨左归饮"异病同治"早发性卵巢功能不全、闭经、绝经综合征的网络药理学研究。方法利用数据库检索获得左归饮活性成分及"异病同治"相关靶点,依托STRING数据库,构建活性成分-靶点网络图和靶点间蛋白-蛋白相互作用(PPI)网络图,并经Cytoscape 3.7.0软件可视化展示;通过DAVID数据库对左归饮"异病同治"交集基因进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,最终通过构建活性成分-靶点-关键通路网络图来展示左归饮"异病同治"相关作用机制。结果筛选出左归饮活性成分127个,相关靶点262个,"异病同治"靶点66个,其主要活性成分为类固醇化合物,干预的PPI核心基因靶点为肿瘤抑制蛋白P53(TP53)、信号传导转录激活因子3(STAT3)、肿瘤坏死因子(TNF)、基因蛋白激酶B1(AKT1)、白细胞介素-6(IL6)等,GO及KEGG富集分析结果主要涉及药物反应、基因表达的正调控、RNA聚合酶Ⅱ启动子转录的正调控、细胞缺氧反应、相同蛋白质结合、酶结合、类固醇受体活性等,其反应主要集中在细胞外液,通过缺氧诱导因子1(HIF-1)信号通路、叉形头转录因子(FoxO)信号通路等发挥作用。结论左归饮"异病同治"的多种类固醇活性成分通过多基因靶点、多信号通路来发挥"异病同治"治疗作用。
Abstract：Objective To investigate the network pharmacological study of Zuoguiyi on premature ovarian insufficiency, amenorrhea and menopausal syndrome. Methods The active ingredients of Zuoguiyin and related targets of "homotherapy for heteropathy" were retrieved by database. Relying on the STRING database, the active ingredient-target network map and protein-protein interaction(PPI) network map among targets were constructed, and visualized by Cytoscape 3.7.0 software. Through David database, gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out on the intersection genes of Zuoguiyin for "homotherapy for heteropathy". Finally, the mechanism of Zuoguiyin′s "homotherapy for heteropathy" was demonstrated through the construction of active component-target-key pathway network diagram. Results A total of 127 Zuoguiyin active ingredient, 262 related targets, and 66 "homotherapy for heteropathy" targets were screened out, in which the main active ingredients are steroid compounds, intervention targets of PPI core gene are tumor suppressor protein P53(TP53), signal transcription activation factor 3(STAT3), tumor necrosis factor(TNF), gene prokinase B1(AKT1),interleukin-6(IL6), etc.; GO and enrichment analysis mainly involve drug reaction, positive regulation of gene expression and positive regulation of transcription of RNA polymerase Ⅱ promoter transcription, cell hypoxia reaction, identical protein binding, enzyme binding, steroid receptor activity and etc; its reaction mainly concentrated in the extracellular fluid, and play a role through the hypoxia-induced factor 1(HIF-1) signaling pathway, and the fork-head transcription factor(Fox O) signaling pathways. Conclusions A variety of active steroid ingredients of Zuoguiyin can exert the therapeutic effect of "homotherapy for heteropathy" through multi-gene target and multi-signal pathway.
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基本信息:
中图分类号:R285
引用信息:
[1]陈衎,唐金艳,马晓蓉,等.左归饮“异病同治”早发性卵巢功能不全、闭经、绝经综合征的网络药理学研究[J].新疆医科大学学报,2021,44(06):744-752.
基金信息:
新疆维吾尔自治区自然科学基金(2019D01C165)
2021-06-15
2021-06-15