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在小鼠中优化多克索鲁比诱导心脏毒性的剂量选择:单剂和多剂方案的综合分析

Min Li¹, Yiyin Zhang¹, Bohan Wu¹

¹Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.

European journal of pharmacology

|July 4, 2025

概括

这项研究提供了基于证据的剂量指南,用于对小鼠的多克索鲁比辛 (DOX) 诱导的心脏毒性. 建议剂量为急性模型的15mg/kg,为慢性模型的特殊方案,以确保可靠的诱导和生存.

科学领域:

药理学和毒理学药理学和毒理学
心血管研究研究心血管研究
临床前模型临床前模型

背景情况:

doxorubicin (DOX) 是一种广泛使用的化疗剂,已知有心脏毒性副作用.
建立可靠的DOX诱导心脏毒性的小鼠模型对于临床前研究至关重要.
需要标准化剂量协议,以确保跨研究的可复制性和可比性.

研究的目的:

在急性和慢性心脏毒性小鼠模型中系统地审查和综合最佳多克索鲁比 (DOX) 剂量的证据.
为在临床前研究中诱导可再生心脏毒性提供基于证据的建议.
确定剂量方案,以平衡心脏毒性诱导与可接受的生存率.

主要方法:

从2015年1月到2024年10月,对多个数据库 (PubMed,科学网,CNKI,万芳,VIP) 的系统文献搜索.
分析了来自736篇文章的808项研究,以确定独特的小鼠模型和剂量方案.
对单剂量和多剂量方案的评估,包括注射剂量,频率,累积剂量和观察到的结果 (心脏毒性,死亡率).

主要成果:

确定了182个独特的DOX诱导心脏毒性的小鼠模型.
对于急性模型,单剂量15-20 mg/kg有效诱导心脏毒性,15 mg/kg显示较低的死亡率.
对于慢性模型,一个常见的方案是每周5毫克/千克4周,或灵活的剂量 (2.5-5.5毫克/千克每剂量,3-6次),累计剂量为15-20毫克/千克.

结论:

在急性多克索鲁比辛 (DOX) 诱导的小鼠心脏毒性时,建议使用15mg/kg的单剂量.
对于慢性心脏毒性,提出了两种方案:标准的每周方案或灵活的累积剂量策略.
这些建议旨在优化心脏毒性诱导,同时在临床前研究中管理动物生存率.

关键词:

急性心脏毒性是什么慢性心脏毒性慢性心脏毒性剂量选择剂量选择德克索鲁比辛是一种多克索鲁比辛.鼠标模型鼠标模型

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