摘要
椎间盘突出症是骨科的高发疾病,而作为其关键病理基础的椎间盘退行性病变(intervertebral disc degeneration,IDD)是一个以细胞外基质进行性降解、结构破坏与生物力学功能丧失为特征的复杂病理过程,不仅在人群中呈现出更高的患病率,更是导致全球人类慢性腰背痛与功能障碍的首要原因,造成了巨大的社会经济负担。尽管构建IDD动物模型对探索该疾病病理机制与推动转化研究具有重要意义,但目前关于IDD的病因与病理生理机制尚未完全阐明,且人类与常见实验动物在脊柱解剖、生物力学及退变病程上存在显著差异,加之现有的IDD动物模型繁杂多样且缺乏统一标准。因此,本指南系统梳理了啮齿类动物、非人灵长类动物以及兔、绵羊/山羊、猪、犬等不同动物的IDD模型,重点阐述三类主流模型的建模原理:诱发性模型(如纤维环/髓核/终板损伤和机械力学损伤)可控性强、周期短,适用于模拟急性损伤与快速筛选疗法;自发性模型能更好地模拟人类与年龄相关的自然退变进程;基因修饰模型则为解析特定分子通路提供了有力工具。指南深入剖析了这些模型的关键技术要点、可重复性与临床相关性,并比较其优势、局限及适用研究场景,旨在引导研究者进行“以科学问题为导向”的精准模型选择。同时,为提升研究结果的深度与可比性,本指南提出了涵盖影像学、组织学、生物化学与分子生物学、生物力学及疼痛行为学等多维度的IDD动物模型实验终点评估体系与推荐观察时间窗,并明确了贯穿实验全程的“替代、减少、优化(replacement,reduction,refinement,3Rs)”伦理原则与动物福利要求。此外,指南还展望了结合单细胞组学、多尺度力学分析及加强疼痛表型评估等未来研究方向。本指南旨在为研究者在具体科学问题与资源条件约束下,如何规范化选择与应用IDD动物模型提供一套系统化、标准化的方法学框架,以期减少研究间的异质性,提升临床前研究成果的转化效率,促进本领域的高质量发展,最终为开发延缓乃至逆转IDD的创新疗法提供坚实的科学基础。
Intervertebral disc herniation is a highly prevalent orthopedic disorder,and intervertebral disc degeneration(IDD),the key pathological basis,is a complex pathological process characterized by progressive degradation of extracellular matrix,structural failure,and loss of biomechanical function,which not only shows higher prevalence in the population,but is also the primary cause of chronic low back pain and dysfunction worldwide,causing a huge socioeconomic burden.Although constructing IDD animal models is important for exploring the pathological mechanisms and promoting translational research of this disease,the etiology and pathophysiological mechanisms of IDD have not been fully elucidated.There are significant differences between humans and common laboratory animals in spinal anatomy,biomechanics,and degenerative course,coupled with the diversity and lack of unified standards of existing IDD animal models.This guide systematically reviews IDD animal models of rodents,non-human primates,as well as different species such as rabbits,goats/sheep,pigs,and dogs,focusing on the modeling principles of three main types of models:inducible models(such as annulus fibrosus/nucleus pulposus/endplate injury and mechanical injury)are suitable for simulating acute injury and rapid screening of therapies due to their high controllability and short cycle;spontaneous models can better simulate the agerelated natural degeneration process in humans;genetically modified models provide powerful tools for analyzing specific molecular pathways.The guideline deeply analyzes the key technical points,reproducibility,and clinical relevance of these models.It also compares their advantages,limitations,and applicable research scenarios to guide researchers to conduct"scientific question-driven"precise model selection.Meanwhile,to improve the depth and comparability of research results,this guideline proposes a multidimensional endpoint evaluation system for IDD animal model experiments covering imaging,histology,biochemistry/molecular biology,biomechanics,and pain-related behavior,with recommended observation time windows.It also clarifies the"3Rs(replacement,reduction,and refinement)"ethical principles and animal welfare requirements throughout the experiment.In addition,the guideline outlines future research directions such as integrating single-cell omics,multiscale mechanical analysis,and strengthening pain-related phenotype assessment.This guideline aims to provide researchers with a systematic and standardized methodological framework for the rational selection and application of IDD animal models under specific scientific questions and resource constraints,in order to reduce inter-study heterogeneity,enhance the translation efficiency of preclinical findings,promote high-quality development in the field,and ultimately provide a solid scientific foundation for developing innovative therapies to delay or even reverse IDD.
出处
《实验动物与比较医学》
2025年第5期524-541,共18页
Laboratory Animal and Comparative Medicine
关键词
椎间盘退行性病变
椎间盘突出
实验动物模型
临床前研究
模型评估
跨物种转化
Intervertebral disc degeneration
Intervertebral disc herniation
Experimental animal model
Preclinical research
Model evaluation
Cross-species translation
