中国药物警戒 ›› 2024, Vol. 21 ›› Issue (8): 871-877.
DOI: 10.19803/j.1672-8629.20240067

• 基础与临床研究 • 上一篇    下一篇

罗沙司他联合当归补血汤对AR和NR3C2基因表达的影响

张凯华1, 刘丁维2, 付长海3, 孙雪林4, 闵先军1,*   

  1. 1中国航天科工集团七三一医院胸外科,北京 100074;
    2青岛市市立医院检验科,山东 青岛 266000;
    3中国航天科工集团七三一医院肾内科,北京 100074;
    4北京医院药学部,国家老年医学中心,中国医学科学院老年医学研究院,北京 100730
  • 收稿日期:2024-01-25 出版日期:2024-08-15 发布日期:2024-08-21
  • 通讯作者: *闵先军,男,硕士,副主任医师,贫血与胸部早癌筛查。E-mail：minxianjun@163.com
  • 作者简介:张凯华,男,硕士,主治医师,贫血与肺恶性肿瘤。
  • 基金资助:
    国家重点研发计划（2020YFC2009000、2009001）; 七三一医院院级科研基金（2022-QSYN-01）

Effects of rosastatin combined with Danggui Buxue Tang on expressions of AR and NR3C2

ZHANG Kaihua1, LIU Dingwei2, FU Changhai3, SUN Xuelin4, MIN Xianjun1,*   

  1. 1Department of Thoracic Surgery, China Aerospace Science & Industry Corporation 731 Hospital, Beijing 100074, China;
    2Medical Laboratory Department, Qingdao Municipal Hospital, Qingdao Shandong 266000, China;
    3Department of Nephrology, China Aerospace Science & Industry Corporation 731 Hospital, Beijing 100074, China;
    4Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
  • Received:2024-01-25 Online:2024-08-15 Published:2024-08-21

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摘要： 目的 基于网络药理学预测罗沙司他联合当归补血汤治疗肾性贫血的作用机制,并进行动物实验验证。方法 运用PharmMapper、TCMSP、STRING、GeneCards、OMIM及DAVID数据库进行靶点蛋白及信号通路分析,探讨罗沙司他联合当归补血汤治疗肾性贫血的潜在作用靶点,构建“药物-靶点-疾病”模型,预测可能的生物途径。进行大鼠实验验证关键靶点和作用机制。结果 网络药理学研究发现,罗沙司他联合当归补血汤主要通过NR3C2、AR、NR1I3和RUNX1T1共4个共同的蛋白靶点,PI3K-Akt等16条共同信号通路发挥治疗肾性贫血的作用。罗沙司他联合当归补血汤通过上调靶蛋白AR表达、抑制靶蛋白NR3C2的表达来发挥作用。结论 罗沙司他联合当归补血汤可通过抑制NR3C2的表达、上调AR的表达来改善机体的炎症及氧化应激,进而发挥治疗肾性贫血的作用。

关键词: 罗沙司他, 当归补血汤, 肾性贫血, 网络药理学, 大鼠

Abstract: Objective To predict the mechanism of roxadustat combined with Danggui Buxue Tang against renal anemia (RA) based on network pharmacology, and to verify the result via animal experiments. Methods The target proteins and signaling pathways were retrieved from PharmMapper, TCMSP, STRING, GeneCards, OMIM and DAVID database. The potential targets of roxadustat combined with Danggui Buxue Tang in treating RA were explored. A “drug-target-pathway” model was established to predict possible biological pathways. Subsequently, rat experiments were conducted to validate the main targets. Results Network pharmacology research found that the combination of roxadustat and Danggui Buxue Tang mainly exerted therapeutic effects on renal anemia through four common protein targets, namely NR3C2, AR, NR1I3, and RUNX1T1, as well as through 16 common signaling pathways such as PI3K-Akt pathway. The combination of roxadustat and Danggui Buxue Tang could upregulate the expression of target protein AR but inhibit the expression of target protein NR3C2 to exert its effects. Conclusion The combination of roxadustat and Danggui Buxue Tang can improve inflammation and oxidative stress in the body by inhibiting the expression of NR3C2 and upregulating the expression of AR, thereby exerting a therapeutic effect on renal anemia.

Key words: roxadustat, Danggui Buxue Tang, renal anemia, network pharmacology, rat

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