眼科 ›› 2025, Vol. 34 ›› Issue (4): 314-318.doi: 10.13281/j.cnki.issn.1004-4469.2025.04.011

• 论著 • 上一篇    下一篇

基于网络药理学探讨苦参碱抗视网膜母细胞瘤的作用机制

张思瑶   练海东   刘佳琳   董星星   袁婷   万慧娟   赵新荣   

  1. 石河子大学第一附属医院眼科,新疆石河子 832008

  • 收稿日期:2024-07-19 出版日期:2025-07-25 发布日期:2025-07-13
  • 通讯作者: 赵新荣,Email:zxr_yk@163.com

Molecular mechanism of matrine in treating retinoblastoma based on network pharmacology

Zhang Siyao, Lian Haidong, Liu Jialin, Dong Xingxing, Yuan Ting, Wan Huijuan, Zhao Xinrong   

  1. Department of Ophthalmology, the First Affiliated Hospital of Shihezi University, Shihezi Xinjiang 832008, China
  • Received:2024-07-19 Online:2025-07-25 Published:2025-07-13
  • Contact: Zhao Xinrong, Email: zxr_yk@163.com

摘要:  目的 应用网络药理学探讨苦参碱抗视网膜母细胞瘤的作用机制。设计  网络药理学分析。研究对象  与苦参碱治疗视网膜母细胞瘤相关的网络数据库文献。方法  从Swiss Target Prediction数据库获得苦参碱的潜在靶点。从GeneCards、OMIM和CTD数据库获得视网膜母细胞瘤相关靶点。建立蛋白质-蛋白质相互作用网络来筛选核心靶点。进行基因本体富集分析及京都基因和基因组百科全书信号通路分析。并通过分子对接技术评估苦参碱和核心靶点之间的相互作用。主要指标 核心靶点。结果  确定了100个苦参碱靶点,获取4419个视网膜母细胞瘤疾病靶点。蛋白质-蛋白质相互作用网络的拓扑分析揭示了6个核心靶点分别为HSP90AA1、HDAC2、BRD4、HDAC6、PARP1、JAK2。GO富集分析显示,生物过程主要包括对酮的反应、细胞对氮化合物的反应和激素水平的调节等;细胞组分主要包括树突和组蛋白衍生物等;分子功能主要包括组蛋白去乙酰化酶活性、神经递质受体活性及生长激素受体结合等。KEGG通路富集分析表明,苦参碱的作用是由病毒致癌机制、凋亡、JAK-STAT和PI3K-Akt等信号通路介导的。分子对接显示苦参碱与筛选的核心靶点之间具有良好的结合能力。结论  苦参碱作用HSP90AA1、HDAC2、BRD4、HDAC6、PARP1和JAK2等靶点,通过调节病毒致癌机制、凋亡、JAK-STAT和PI3K-Akt等信号通路发挥抗视网膜母细胞瘤作用。

关键词: 苦参碱, 视网膜母细胞瘤, 网络药理学

Abstract:  Objective  In order to explore the molecular mechanism of matrine in treating retinoblastoma based on network pharmacological analysis. Design  Network pharmacology analysis. Participants  Network database literatures related to the treatment of retinoblastoma with matrine. Methods Taking matrine as the object, the corresponding potential drug targets in matrine were obtained from Swiss Target Prediction database. Retinoblastoma-related targets were collected through the GeneCards, OMIM, and CTD database. Furthermore, core targets were screened by establishing protein-protein interaction (PPI) networks. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. Finally, the molecular docking calculation was performed to evaluate the interaction between matrine and core targets. Main Outcome Measures  Core targets. Results  Matrine contained 100 targets. A total of 4419 targets for retinoblastoma were obtained. The topology analysis results of the PPI network showed that 6 main targets such as HSP 90AA1, HDAC2, BRD4, HDAC6, PARP1, JAK2. GO enrichment analysis found that Biological process (BP) mainly includes response to ketone, cellular response to nitrogen compound and regulation of hormone levels, etc; Cell components(CC) mainly include dendrite and histone deacety lase complex, etc; Molecular functions(MF) mainly include histone deacety lase activity, neurotransmitter receptor activity and growth hormone receptor binding. KEGG pathway analysis showed that it involved viral carcinogenesis, necroptosis, JAK-STAT signaling pathway, and PI3K-Aktsignaling pathway, etc. Molecular docking showed that matrine had good binding with the core targets. Conclusions  Matrine acts on targets such as HSP90AA1, HDAC2, JAK2, BRD4, HDAC6, and PARP1, and exerts therapeutic effects on retinoblastoma by regulating viral carcinogenesis, necroptosis, JAK-STAT signaling pathway, and PI3K-Aktsignaling pathway, etc.

Key words:  Matrine, Retinoblastoma, Network pharmacology