Lotz Jeffrey C
Orthopaedic Bioengineering Laboratory, Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143-0514, USA.
Spine (Phila Pa 1976). 2004 Dec 1;29(23):2742-50. doi: 10.1097/01.brs.0000146498.04628.f9.
A literature review of intervertebral disc degeneration animal models.
Focus is placed on those models that suggest degeneration mechanisms relevant to human.
Medical knowledge from observational epidemiology and intervention studies suggest many etiologic causal factors in humans. Animal models can provide basic science data that support biologic plausibility as well as temporality, specificity, and dose-response relationships.
Studies are classified as either experimentally induced or spontaneous, where experimentally induced models are subdivided as mechanical (alteration of the magnitude or distribution of forces on the normal joint) or structural (injury or chemical alteration). Spontaneous models include those animals that naturally develop degenerative disc disease.
Mechanobiologic relationships are apparent as stress redistribution secondary to nuclear depressurization (by injury or chemical means) can cause cellular metaplasia, tissue remodeling, and pro-inflammatory factor production. Moderate perturbations can be compensated for by cell proliferation and matrix synthesis, whereas severe perturbations cause architectural changes consistent with human disc degeneration.
These models suggest that two stages of architectural remodeling exist in humans: early adaptation to gravity loading, followed by healing meant to reestablish biomechanical stability that is slowed by tissue avascularity. Current animal models are limited by an incomplete set of initiators and outcomes that are only indirectly related to important clinical factors (pain and disability).
椎间盘退变动物模型的文献综述。
重点关注那些提示与人类相关退变机制的模型。
来自观察性流行病学和干预研究的医学知识提示人类存在多种病因。动物模型可以提供支持生物学合理性以及时间性、特异性和剂量反应关系的基础科学数据。
研究分为实验诱导型或自发型，其中实验诱导型模型又细分为机械型（改变正常关节上力的大小或分布）或结构型（损伤或化学改变）。自发型模型包括那些自然发生椎间盘退变疾病的动物。
机械生物学关系很明显，因为核减压（通过损伤或化学方法）继发的应力重新分布可导致细胞化生、组织重塑和促炎因子产生。适度的扰动可通过细胞增殖和基质合成来代偿，而严重的扰动则会导致与人类椎间盘退变一致的结构变化。
这些模型提示人类存在两个结构重塑阶段：早期适应重力负荷，随后是旨在重新建立生物力学稳定性的愈合过程，但由于组织无血管性而减缓。当前的动物模型受到一组不完整的启动因素和结果的限制，这些因素仅与重要的临床因素（疼痛和残疾）间接相关。
