中国药物警戒 ›› 2024, Vol. 21 ›› Issue (6): 606-610.
DOI: 10.19803/j.1672-8629.20230682

• 中药毒性早期发现及机制研究专栏 • 上一篇    下一篇

附子中次乌头碱调控miR-134对心肌细胞hERG通道的影响

葛运炫1,2, 王宇光2, 张卓2, 马增春2#, 高月1,2*   

  1. 1北京工业大学环境与生命学部,北京 100124;
    2军事医学研究院辐射医学研究所,北京 100850
  • 收稿日期:2023-11-02 出版日期:2024-06-15 发布日期:2024-06-18
  • 通讯作者: *高月,女,博士,研究员·博导,中药药理与毒理学。E-mail: gaoyue@bmi.ac.cn; #为共同通信作者。
  • 作者简介:葛运炫,男,在读博士,生物医药工程。
  • 基金资助:
    国家自然科学基金资助项目（82192911、81630102）; 国家重点研发计划（2022YFC3500303）; 国家中医药传承创新团队方剂配伍和方药作用机理创新团队

Effect of hypaconitine of radix aconiti carmichaeli on hERG channels in cardiac myocytes via miR-134 regulation

GE Yunxuan1,2, WANG Yuguang2, ZHANG Zhuo2, MA Zengchun2#, GAO Yue1,2,*   

  1. 1Faculty of Environment and Life Sciences, Beijing University of Technology, Beijing 100124, China;
    2Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China
  • Received:2023-11-02 Online:2024-06-15 Published:2024-06-18

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摘要： 目的 从miRNA-hERG途径探索双酯型生物碱对心肌细胞毒性的调控机制。方法 采用全细胞膜片钳技术测定hERG电流,实时荧光定量PCR测定基因表达水平,蛋白质免疫印迹实验测定蛋白表达。结果 3种双酯型生物碱均可降低hERG蛋白和基因表达水平,抑制心肌细胞hERG通道开放率,次乌头碱抑制作用最为显著且呈剂量依赖性。次乌头碱促进miR-134表达量上升最明显,抑制miR-134表达后hERG蛋白基因表达水平显著上升,hERG蛋白基因表达抑制率降低。结论 通过对miRNA表达进行修饰,次乌头碱可抑制hERG蛋白基因表达水平及hERG通道开放,此抑制效果可能是附子心脏毒性的重要组成部分。

关键词: 附子, 次乌头碱, 心肌细胞, 心肌毒性, hERG通道, miRNA, miR-134, 蛋白, 基因, 表达

Abstract: Objective To explore the mechanism by which hypaconitine regulates myocardial cell toxicity through miRNA-hERG pathway. Methods The gene expression level was measured by real-time fluorescence quantitative PCR, the protein expression was determined by Western blot, and hERG currents were recorded by the whole cell patch-clamp technique. Results Three major diester alkaloids could inhibit hERG protein and gene expressions, among which hypaconitine had the strongest inhibitory effect in a dose-dependent manner. Hypaconitine promoted the expression of miR-134 most significantly and the weakened inhibitory effect of hypaconitine on hERG protein gene was exhibited after the expression of miR-134 was decreased. Conclusion Hypoaconitine can decrease the rate of hERG channel inactivation and the expression of hERG by upregulating the expressions of related miRNAs. The inhibitory effect of hypaconitine on hERG may be an important cause of radix aconiti carmichaeli cardiotoxicity.

Key words: radix aconiti carmichaeli, hypaconitine, cardiomyocyte, myocardial toxicity, hERG pathway, miRNA, miR-134, protein, gene, expression

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