建立椎间盘退变动物模型的方法学回顾

Retrospection of establishing animal models with intervertebral disc degeneration in methodology

目的:对国内外近年来建立椎间盘退变动物模型的方法及原理进行回顾,并对比各种方法的优缺点及临床相关性,探讨具有操作方法简便,可重复性强的椎间盘退变动物模型建立方法。资料来源:应用计算机检索Medline1998-01/2004-08的与椎间盘退变动物模型相关的文献,检索词“animalmodel,intervertebraldiscdegeneration”,并限定文献语种为英文。资料选择:对资料进行初审,然后筛除非随机临床试验的研究,对剩余的文献开始查找全文,以是否为随机对照临床试验作为纳入标准。资料提炼:共收集到15篇关于建立椎间盘退变动物模型的随机和非随机试验研究,14篇文献为随机对照临床试验,纳入综述,排除1篇为非随机试验研究。14篇文献包括448个实验对象,通过对不同的建模方法进行分类,并对不同分组模型优缺点及临床相关性进行评定。资料综合:椎间盘退变模型可以划分为实验诱发和自发性模型,实验诱发的动物模型又可以细分为机械型(应力型、脊柱不稳致椎间盘退变模型)和结构型(手术直接损伤型、化学损伤型)。①应力动物模型:外部压力作用于椎间盘,导致内部应力的重新分配,随后在局部出现生物学效应。②脊柱不稳致椎间盘退变动物模型:通过手术间接破坏关节面或棘突等支撑组织,反复刺激脊柱肌肉或进行脊柱相邻节段融合等方法间接对脊柱施加过度运动而实现。③手术直接损伤型动物模型:通过外科手术的方法干扰纤维环或终板引发间盘的退变是目前广泛应用的一种建模方法。④化学损伤型动物模型:旨在通过选择性的降解蛋白多糖减少间盘容积从而达到减轻受累神经根压力的作用。通过注入木瓜凝乳蛋白酶的治疗方法已经在兔和狗的动物实验中得以证实。⑤自发性模型:一些特殊的动物种系中,随着年龄的增加,椎间盘的水分、固定电荷密度和膨胀压逐渐降低,而在脊柱周围肌肉和椎体松质骨中无此变化。自发间盘退变的动物模型主要是间盘形态功能之间不稳定的平衡,遗传因素的影响可以改变这种平衡而加速退变。结论:椎间盘退变动物模型具有一定的局限性,表现在观察时间相对较短,部分观察指标无法监测。小动物椎间盘退变模型与人椎间盘退变之间存在差距,但通过大鼠和兔的椎间盘退变模型仍可对人椎间盘进行很好的研究。

OBJECTIVE： To review the method and principle of establishing animal models with intervertebral disc degeneration at home and abroad at present, compare the advantage and disadvantage of various methods and its clinical correlation and explore the establishing method, which is easy to use and with strong reliability in animal models with intervertebral disc degeneration. DATA SOURCES： The Medline database was searched for articles about animal models with intervertebral disc degeneration published between January 1998 and August 2004 with the key words of ＂animal model, intervertebral disc degeneration＂ in English. STUDY SELECTION： The data were selected firstly, and then studies on non-randomized clinical trials were excluded. The full-texts of leftover were retrieved. Inclusive criteria were whether studies on randomized controlled clinical trial or not. DATA EXTRACTION： A total of 15 articles on randomized and nonrandomized establishing animal models with intervertebral disc degeneration trials were collected. Fourteen literatures on randomized controlled clinical trial were included in the review, and 1 article on nonrandomized controlled clinical trial was excluded. In the 14 literatures, there were 448 experimental subjects. The advantage and disadvantage of different grouping models and its clinical correlation were evaluated by the classification of different methods of establishing models. DATA SYNTHESIS： Models with intervertebral disc degeneration could be divided into experimental induced models and spontaneous models. Experimental induced models also could be assigned into mechanical model （stress model and unstable spine-induced intervertebral disc degeneration model） and structure model （operation injured model and chemical injured model） in detail. ①Stress model： Effect of outside pressure on intervertebral disc led to redistribution of internal stress, followed by local biological effect. ②Unstable spine-induced intervertebral disc degeneration model： Shoring tissues, such as articular facet or spinous process, etc, were destroyed in operation, which became true by giving overexercise on spine directly with repeated stimulation on muscle of spine or confluence at close segment of spine, etc. ③Operation injured model： Degeneration of disc induced by interfering fibrous rings or end plate by surgery operation was a common used metuod to establish models. ④ Chemical injured model： Volume of disc was reduced by selectively degrading proteoglycan so as to relieve the pressure of involved nerve roots. The therapeutical method of injecting chymopapain had been confirmed in the animal experiment with rabbits and dogs. ⑤ Spontaneous model： In some special germ line, moist, density of fixed charge and oncotic pressure in intervertebral disc decreased with the increase of age, while there was no change around muscle of spine and spongy bone of vertebral body. Spontaneous model with intervertebral disc degeneration was the balance of unstability in medal function, while the effect of genetic factor could change this balance and accelerate the degeneration. CONCLUSION： Animal models with intervertebral disc degeneration have certain limitation, showing short observational time and part of observational index cannot be monitored. Small animal models with intervertebral disc degeneration have distance with human with intervertebral disc degeneration. But intervertebral disc of human can be studied fully by observing intervertebral disc degeneration in rats and rabbits.