中国药物警戒 ›› 2025, Vol. 22 ›› Issue (5): 532-538.
DOI: 10.19803/j.1672-8629.20250021

• 免疫细胞介导的药物性肝损伤研究专栏 • 上一篇    下一篇

固有型药物性肝损伤中肝实质细胞的适应性反应研究进展

陈清钰1, 江振洲1#, 张陆勇1,2,*   

  1. 1中国药科大学多靶标天然药物全国重点实验室新药筛选与药效评价中心,江苏 南京 210009;
    2广东药科大学新药研发中心,广东 广州 510006
  • 收稿日期:2025-01-09 出版日期:2025-05-15 发布日期:2025-05-19
  • 通讯作者: *张陆勇,男,博士,教授·博导,分子药理学与毒理学。E-mail:lyzhang@cpu.edu.cn;#为共同通信作者。
  • 作者简介:陈清钰,女,在读硕士,药理学。
  • 基金资助:
    国家自然科学基金资助项目(82274200、82074114、81973562、81773995)

Research Progress in Adaptive Response of Hepatocytes in Intrinsic Drug-Induced Liver Injury

CHEN Qingyu1, JIANG Zhenzhou1#, ZHANG Luyong1,2,*   

  1. 1New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing Jiangsu 210009, China;
    2Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou Guangdong 510006, China
  • Received:2025-01-09 Online:2025-05-15 Published:2025-05-19

摘要: 目的 归纳肝实质细胞通过适应性反应对抗固有型药物性肝损伤的研究进展,为具有潜在肝毒性的药物提供安全用药参考。方法 从药物代谢模式、线粒体应激反应、肝细胞增殖方面阐述适应性反应减轻固有型药物性肝损伤的机制。结果 药物导致肝损伤发生的同时将激活适应性反应,通过增加解毒代谢、降低毒性代谢、促进线粒体自噬、增强抗氧化系统、促进肝细胞增殖、调节存活肝细胞功能性基因表达等方法维持肝功能稳态,降低固有型药物性肝损伤程度。结论 适应性反应机制复杂,在固有型药物性肝损伤中发挥重要的内源性保护作用。对适应性反应的研究可为有潜在肝毒性的药物提供临床安全合理用药方案和为固有型药物性肝损伤的治疗与预防提供参考。

关键词: 固有型药物性肝损伤, 适应性反应, 药物代谢酶, 线粒体应激反应, 肝再生

Abstract: Objective To summarize the research progress in the adaptive response of hepatocytes against intrinsic drug-induced liver injury so as to provide a safe medication regimen for drugs with potential hepatotoxicity. Methods By searching databases for related literature published as of January 10, 2025, the mechanism by which adaptive response of hepatocytes helped alleviate intrinsic drug-induced liver injury was studied in terms of drug metabolism, mitochondrial stress response and hepatocyte proliferation. Results Drug-induced liver injury coincided with the activation of adaptive response that was believed to maintain liver homeostasis and mitigate intrinsic drug-induced liver injury by increasing detoxification metabolism, reducing toxic metabolism, promoting mitophagia, enhancing the antioxidant system, promoting hepatocyte proliferation, and regulating functional gene expressions in surviving hepatocytes. Conclusion The mechanism of adaptive response is complex and plays an important role in endogenous protection against intrinsic drug-induced liver injury. The study of adaptive response can provide a clinically safe and rational regimen for potentially hepatotoxic drugs and facilitate the treatment and prevention of intrinsic drug-induced liver injury.

Key words: Intrinsic Drug-Induced Liver Injury, Adaptive Response, Drug Metabolizing Enzymes, Mitochondrial Stress Response, Liver Regeneration

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