几种椎间盘退变动物模型的建立和应用

椎间盘退变是一种年龄相关的退行性疾病,是引起下腰痛的主要因素,严重影响病人的生活质量,并显著增加家庭的经济负担。目前,缺少椎间盘退变的有效干预和治疗手段,部分原因是其发病机制尚未阐明。椎间盘退变动物模型的构建对于阐明该疾病的病理机制至关重要。椎间盘退变是一个复杂的过程,受机械应力、结构损伤、生物化学与基因表达等多种因素的影响。本文总结了应用异常机械应力、结构损伤、生物化学或化学诱导和基因敲除等方式构建的椎间盘退变动物模型。生物力学是维持椎间盘稳态的重要因素,异常的机械应力会导致椎间盘退变。同时,椎间盘退变常伴随结构性损伤,椎间盘结构破坏也会导致椎间盘发生退变。此外,生物化学或化学诱导和关键基因敲除也会导致椎间盘退变。本文按照造成异常机械应力的因素将机械应力模型分为加压模型和失稳模型;按照椎间盘结构将结构损伤模型分为髓核与纤维环损伤模型和软骨终板损伤模型。总结了生物化学或化学诱导模型以及新型的基因敲除模型。讨论了不同类型椎间盘退变动物模型的可能应用和局限性。

Establishment and Application of Several Animal Models for the Study of Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) is an age-related degenerative disease and a major cause of low back pain. IDD greatly impairs the quality of life of patients and dramatically increases the economic burden of patient families. There are currently no effective intervention and treatment for IDD, partly due to a lack of understanding of its pathogenesis. The establishment and characterization of IDD animal models are critical for defining mechanisms underlying its pathogenesis. IDD is a complex process, which is affected by mechanical stress, injury, biochemistry and gene expression. In this review article, we summarize several IDD animal models generated by utilizing abnormal mechanical stress, injury, biochemical and chemical induction and gene knockout. Biomechanics play a key role in maintaining intervertebral disc homeostasis, and abnormal mechanical stress can cause IDD. Usually, IDD is accompanied by structural injury which exacerbates IDD. In addition, biochemical and chemical induction and knockout of key genes can also lead to IDD. Among the different factors causing abnormal mechanical stress, there are two mechanical stress models: pressure model and instability model. According to the structure of intervertebral disc, there are two structural injury models: the nucleus pulposus and annulus fibrosus injury model and the cartilage endplate injury model. The biochemical and chemical induction model and the gene knockout model are summarized, and the applications and limitations of different IDD animal models are discussed.