基于数据挖掘与网络药理学探究中医药改善子宫内膜容受性的用药规律及作用机制
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R714.8

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国家自然科学基金项目(82074480,82274567);浙江省中医药科技计划项目(2025ZR176,2025ZS003);杭州市红十字会医院博士 科研启动基金项目(HHBJ2024001)


Medication Rule and Mechanism of Chinese Medicine to Improve Endometrial Receptivity Based on Data Mining and Network Pharmacology
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    摘要:

    目的:基于数据挖掘与网络药理学探究中医药改善子宫内膜容受性(ER) 的组方用药规律及潜在 作用机制。方法:以ER为主题,通过中国知网、万方学术期刊全文数据库、维普中文科技期刊数据库检索相 关文献。依据限定条件筛选后,应用Microsoft Excel 2019 软件建立数据库,计算药物使用频次,应用SPSS Modeler 18.0软件进行关联规则分析及复杂网络构建,应用SPSS Statistics 26.0软件进行系统聚类分析。归纳中 医药改善ER的用药规律及配伍关系;通过中药系统药理学平台与SwissTargetPrediction数据库获取核心药物的活 性成分及靶点,在GeneCards数据库中获取ER低下的潜在作用靶点,将核心药物与ER低下的交集靶点导入 String数据库和Cytoscape 3.7.1软件获取关键靶点,对交集靶点进行基因本体(GO) 功能富集分析和京都基因 与基因组百科全书(KEGG) 通路富集分析。结果:通过检索文献,筛选出方剂130首,中药159味,使用 频次较高的4味中药依次为菟丝子、当归、熟地黄、丹参;关联规则分析结果显示菟丝子、当归、熟地黄、丹 参是改善ER的核心药物;聚类分析获得养血、温阳、滋阴3类药物组合。对“菟丝子-当归-熟地黄-丹参”进 行网络药理学分析,获取45个核心药物与ER低下的交集靶点,10个关键靶点。GO功能富集分析结果显示, 核心药物改善ER可能通过影响激素反应、细胞迁移与细胞运动的正向调节等生物过程,膜筏、转录调节因子 复合物等细胞组分,激素结合、转录因子结合等分子功能发挥作用。KEGG通路富集分析结果显示,核心药物 可能通过磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt) 信号通路、缺氧诱导因子-1(HIF-1) 信号通路、血管内 皮生长因子(VEGF) 信号通路、叉头框蛋白O(FOXO) 信号通路等改善ER。结论:中医药改善ER以补肾填 精、养血活血为主,核心药物菟丝子-当归-熟地黄-丹参可能通过肿瘤坏死因子、丝氨酸/苏氨酸激酶1、白细 胞介素1β等靶点,调控PI3K/Akt、HIF-1、VEGF、FOXO及细胞衰老、凋亡、自噬等信号通路,减轻炎症反 应、促进血管生成、调节蜕膜化等,发挥改善ER的作用,为中医药提高体外受精-胚胎移植成功率提供数据 支持及理论依据。

    Abstract:

    Abstract:Objective:To explore the medication rule and potential mechanism of Chinese medicine in improving endometrial receptivity (ER) based on data mining and network pharmacology. Methods:The ER-relevant literature was retrieved through the China National Knowledge Infrastructure,the Wanfang Date,and the VIP Chinese Science Journals Database. After screening according to the limited conditions, Microsoft Excel 2019 software was used to establish a database; the frequency of medicinals use was calculated; SPSS Modeler 18.0 software was used for association rule analysis and complex network construction; SPSS Statistics 26.0 software was used for systematic cluster analysis. Therefore, the medication rules and compatibility of Chinese medicine to improve ER were summarized. Furthermore,the active ingredients and targets of core medicinals were obtained through the TCM System Pharmacology Platform and the SwissTargetPrediction database. Potential targets of low ER were obtained from the GeneCards database. The intersection targets of core medicinals and low ER were imported into the String database and Cytoscape 3.7.1 to obtain the key targets. Gene Ontology( GO) and Kyoto Encyclopedia of Genes and Genomes( KEGG) enrichment analysis of the intersection targets were further carried out. Results: Through the literature search, 130 formulas and 159 Chinese medicinals were screened and summarized to improve ER. The four Chinese medicinals with high frequency of use were Cuscutae Semen, Angelicae Sinensis Radix, Rehmanniae Radix Praeparata, and Salviae Miltiorrhizae Radix et Rhizoma. The association rules showed that Cuscutae Semen,Angelicae Sinensis Radix, Rehmanniae Radix Praeparata, and Salviae Miltiorrhizae Radix et Rhizoma were the core medicinals to improve ER. Cluster analysis divided Chinese medicinals into three categories: blood nourishment, warming yang, and yin nourishment. Network pharmacological analysis of " Cuscutae Semen- Angelicae Sinensis Radix- Rehmanniae Radix Praeparata- Salviae Miltiorrhizae Radix et Rhizoma " was carried out,and 45 intersecting targets of core medicinals and low ER,as well as 10 key targets,were obtained. The results of GO functional enrichment analysis showed that the core medicinals may improve ER by affecting the biological processes such as response to hormones and positive regulation of cell migration and motility, cellular components such as membrane raft and transcription regulator complex, and molecular functions such as hormone binding and transcription factor binding. The results of KEGG pathway enrichment analysis showed that the core medicinals may improve ER through phosphatidylinositol 3-kinase/protein kinase B( PI3K/ Akt) signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway,forkhead frame protein O (FOXO) signaling pathway,etc. Conclusion:Chinese medicine can improve ER by supplementing the kidney and essence,and nourishing and invigorating blood. The core medicinals "Cuscutae Semen, Angelicae Sinensis Radix, Rehmanniae Radix Praeparata, and Salviae Miltiorrhizae Radix et Rhizoma" may regulate PI3K/Akt,HIF-1,VEGF,FOXO as well as cell senescence,apoptosis,autophagy and other signaling pathways through tumor necrosis factor,serine/threonine kinase,interleukin-1β and other targets, thereby reducing inflammation, promoting angiogenesis, regulating decidualization, and ultimately playing a role in improving ER,which provides data support and theoretical basis for Chinese medicine to improve the success rate of in vitro fertilization-embryo transfer.

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郑志博,刘雁峰,李影,陈洁,侯婷婷,丁彩飞,江雪娟.基于数据挖掘与网络药理学探究中医药改善子宫内膜容受性的用药规律及作用机制[J].新中医,2025,57(1):192-200

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  • 在线发布日期: 2025-01-14
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