PDK4调控“内质网-线粒体对话”关联阿霉素心脏毒性研究进展

doi:10.19803/j.1672-8629.20250272

中国药物警戒 ›› 2025, Vol. 22 ›› Issue (8): 863-868.
DOI: 10.19803/j.1672-8629.20250272

• 药源性心脏毒性预警研究专栏（一） • 上一篇下一篇

PDK4调控“内质网-线粒体对话”关联阿霉素心脏毒性研究进展

史彦蕾^1,2, 张冰^3,4, 王雨², 许卓欣^1,2, 田敏², 孟敏^2*, 萨日娜^2,3#

¹甘肃中医药大学药学院,甘肃兰州 730000;
²甘肃省人民医院药剂科,甘肃兰州 730000;
³甘肃省人民医院岐黄学者张冰工作室,甘肃兰州 730000;
⁴北京中医药大学中药学院,北京 102488

收稿日期:2025-04-29 出版日期:2025-08-15 发布日期:2025-08-13
通讯作者: ^*孟敏,女,博士,主任药师,天然产物活性成分。E-mail: min_pharmacy@163.com ^#为共同通信作者。
作者简介:史彦蕾,女,在读硕士,中药功效与安全性评价。
基金资助:
国家自然科学基金资助项目（82274117）; 甘肃省卫生健康行业科研项目（GSWSQN2023-07）; 甘肃省中医药管理局高水平重点课题（GZKZ-2024-17）; 甘肃省卫生健康行业科研项目优秀青年人才项目（GSWSQN2024-13）; 甘肃省人民医院院内科研基金项目青年培训项目（23GSSYF-34）

Doxorubicin-Induced Cardiotoxicity Related to Regulation of Mitochondrial-Associated Membranes by PDK4

SHI Yanlei^1,2, ZHANG Bing^3,4, WANG Yu², XU Zhuoxin^1,2, TIAN Min², MENG Min^2*, SA Rina^2,3#

¹School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou Gansu 730000, China;
²Department of Pharmacy, Gansu Provincial Hospital, Lanzhou Gansu 730000, China;
³Zhang Bing’s Studio of Qi-Huang Scholars, Gansu Provincial Hospital, Lanzhou Gansu 730000, China;
⁴School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102400, China

Received:2025-04-29 Online:2025-08-15 Published:2025-08-13

摘要/Abstract

摘要： 目的分析PDK4调控内质网-线粒体接触位点（Mitochondria-Associated Membranes, MAMs）即“内质网-线粒体对话”的分子机制,并探讨其与蒽环类药物心脏毒性的潜在关联,为研发心脏保护策略提供理论依据。方法通过对近年来相关文献的检索和分析,系统综述了PDK4在MAMs中的作用机制,及其在蒽环类药物心脏毒性中的作用。结果研究发现,PDK4、MAMs及蒽环类药物心脏毒性之间存在复杂的相互作用,主要体现在能量代谢障碍、氧化应激、细胞凋亡和钙稳态失衡等方面,这些相互作用在蒽环类药物心脏毒性的发展过程中发挥重要作用。结论 PDK4通过过表达,主要破坏MAMs介导的钙稳态,造成线粒体钙超载,进而影响蒽环类药物心脏毒性,这为开发针对蒽环类药物心脏毒性的保护策略提供思路和潜在靶点。

关键词: 蒽环类药物, PDK4, 心脏毒性, 内质网-线粒体接触位点, 线粒体功能障碍, 钙稳态

Abstract: Objective To analyze the molecular mechanism through which PDK4 regulates Mitochondria-Associated Membranes(MAMs) and explore its potential association with anthracycline-induced cardiotoxicity in order to provide data for developing cardioprotective strategies. Methods By reviewing recent literature, the role of PDK4 in MAMs and its potential involvement in anthracycline-induced cardiotoxicity was explored. Results There were complicated interactions between PDK4, MAMs, and anthracycline-induced cardiotoxicity, primarily manifested as energy metabolism disorders, oxidative stress, apoptosis, and calcium homeostasis imbalance. These interactions played a significant role in the progression of anthracycline-induced cardiotoxicity. Conclusion Overexpression of PDK4 can, above all, disrupt calcium homeostasis mediated by MAMs, leading to mitochondrial calcium overload and consequently exacerbating anthracycline-induced cardiotoxicity. This study can offer novel insights and help identify potential therapeutic targets for developing protective strategies against anthracycline-associated cardiotoxicity.

Key words: Anthracyclines, PDK4, Cardiotoxicity, Mitoch-ondria-Associated Membranes(MAMS), Mitochondrial Dysfunction, Calcium Homeostasis

中图分类号:

R994.13
R972

史彦蕾, 张冰, 王雨, 许卓欣, 田敏, 孟敏, 萨日娜. PDK4调控“内质网-线粒体对话”关联阿霉素心脏毒性研究进展[J]. 中国药物警戒, 2025, 22(8): 863-868.

SHI Yanlei, ZHANG Bing, WANG Yu, XU Zhuoxin, TIAN Min, MENG Min, SA Rina. Doxorubicin-Induced Cardiotoxicity Related to Regulation of Mitochondrial-Associated Membranes by PDK4[J]. Chinese Journal of Pharmacovigilance, 2025, 22(8): 863-868.

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https://zgywjj.magtechjournal.com/CN/Y2025/V22/I8/863

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PDK4调控“内质网-线粒体对话”关联阿霉素心脏毒性研究进展

Doxorubicin-Induced Cardiotoxicity Related to Regulation of Mitochondrial-Associated Membranes by PDK4

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