动物替代新方法学在生物医学领域的应用及其对“3R”原则的践行

doi:10.12300/j.issn.1674-5817.2025.164

摘要/Abstract

摘要：

实验动物是生命科学、医学研究及药物研发过程中常用的体内模型，其使用日益广泛，相关的伦理与福利问题也愈发引人关注。“3R”原则（替代、减少、优化）作为开展动物实验应遵循的黄金准则已被广泛认可，为平衡科学研究与动物福利提供了指导。本文所指新方法学是一类贴近人体生理系统、可替代或减少传统动物实验的技术，主要包括体外方法（如类器官、器官芯片、3D生物打印）、化学方法及计算模型等。本文综述了各类新方法学的技术特点、发展历程及其在疾病建模、药物研发、毒理学评估等领域的应用进展，并重点分析其对“3R”原则的践行路径。新方法学可通过体外仿生模型实现部分动物实验的替代，通过高通量筛选与计算模拟减少实验动物使用数量，通过精准剂量预测与早期生物标志物监测优化实验设计、减轻动物痛苦。新方法学目前还面临不能完全还原人体复杂生理系统、标准化与可重复性不足、认可体系与验证路径不成熟等挑战。相信通过持续的技术创新、严谨的科学验证、积极的国际合作以及健全的政策支持，新方法学有望逐步减少传统动物实验，推动生物医学研究向“科学严谨—动物福利—经济高效”协同发展的方向迈进。

关键词: 新方法学, “3R”原则, 类器官, 器官芯片, 3D生物打印, 计算模型, 实验动物伦理

Abstract:

Laboratory animals are increasingly utilized as in vivo models for life sciences, medical research, and drug development, and the associated ethical and welfare issues have attracted increasing attention. The "3R" principle (replacement, reduction, refinement) is a globally recognized guideline for conducting animal experiments, providing direction for balancing scientific research with animal welfare. New approach methodologies refer to technologies that mimic human physiological systems and can replace or reduce traditional animal experiments, mainly including in vitro (e.g., organoids, organ-on-a-chip,3D bioprinting models), in chemico, and in silico tools. This review systematically examines the technical characteristics, development history, and applications of new approach methodologies in disease modeling, drug development, toxicological evaluation, etc., and focuses on the implementation path of the "3R" principle. New approach methodologies can replace some animal experiments through in vitro biomimetic models, reduce the number of experimental animals used through high-throughput screening and computational simulation, optimize experimental design and alleviate animal suffering through accurate dose prediction and early biomarker monitoring. New approach methodologies still face challenges such as the inability to fully recapitulate the complex human physiological system, insufficient standardization and reproducibility, and underdeveloped validation and acceptance pathways. With continuous technological innovation, rigorous scientific validation, proactive international cooperation, and sound policy support, new approach methodologies are expected to gradually reduce the use of traditional animal experiments and advance biomedical research toward the coordinated pursuit of scientific rigor, animal welfare, and cost-effectiveness.

Key words: New approach methodologies, "3R" principle, Organoids, Organ-on-a-chip, 3D bioprinting models, In silico tools, Laboratory animal ethics

中图分类号:

Q95-33

王璐,王青杰,杨春弘,等. 动物替代新方法学在生物医学领域的应用及其对“3R”原则的践行[J]. 实验动物与比较医学, 2026, 46(4): 573-582. DOI: 10.12300/j.issn.1674-5817.2025.164.

WANG Lu,WANG Qingjie,YANG Chunhong,et al. Application of New Approach Methodologies in Biomedical Field and Their Implementation of "3R" Principle[J]. Laboratory Animal and Comparative Medicine, 2026, 46(4): 573-582. DOI: 10.12300/j.issn.1674-5817.2025.164.

图/表 1

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