目的:通过直立体位下无创性轴向加载的方式,建立一种新型兔腰椎间盘早期退变的动物模型。方法:24只4月龄雄性新西兰大白兔随机分为实验组及对照组。将实验组动物置于特制筒内使之保持直立体位,并自颈部施以600g轴向载荷,每日6h;对照组动物不接受任何处理而常规饲养。在实验开始前及实验开始后4周、8周、12周时对全部动物行X线及MRI检查,观察实验组动物在筒内时腰椎的骨性结构,通过椎间盘高度指数(disc height index,DHI)测量,比较两组动物侧卧位时L2/3、L4/5和L6/7节段椎间隙高度改变;通过髓核相对灰度值测量比较两组动物髓核含水量变化。14周后全部动物处死,取L5/6节段胶冻状髓核组织,应用rtPCR检测Ⅰ型胶原、Ⅱ型胶原及蛋白多糖表达水平;取L6/7节段椎间盘连同上、下各1mm软骨下骨,应用HE及天狼星红染色观察各组动物椎间盘组织结构改变。结果:2只实验组动物在实验过程中死亡,其对应的实验数据从结果中剔除。腰椎X线片显示,在直立体位负重条件下,实验组兔腰椎形成明显后凸,较侧卧位下腰椎间隙明显变窄,在L2/3节段,直立体位下椎间隙高度为侧卧位时的75.1%(P<0.05);在L4/5节段为54.8%(P<0.05);在L6/7节段为47.9%(P<0.05)。DHI测量显示两组动物腰椎各节段DHI在任何时间点均无显著差异(P>0.05)。MRI结果显示,在L2/3节段,实验组与对照组髓核灰度值在任何时间点均无统计学差异(P>0.05),在L4/5节段,实验组与对照组髓核相对灰度值在12周时开始具有显著差异(P<0.05);在L6/7节段,两组间在8周时即开始有显著性差异(P<0.05)。rt-PCR结果显示,实验组Ⅰ型胶原m RNA表达明显高于对照组(3.57倍,P<0.05);而Ⅱ型胶原及蛋白多糖表达明显低于对照组(分别为0.35倍和0.43倍,P<0.05)。病理学检查显示对照组与实验组椎间盘组织结构存在显著差异,对照组髓核组织与纤维环间边界清晰,髓核内富含均匀分布的髓核细胞;实验组内层纤维环明显增生,而髓核区域相应减小。结论:直立体位下无创性轴向加载方式可显著加速兔腰椎间盘的退变进程,其在发病机理上与人类椎间盘退变更加相似,该腰椎间盘退变动物模型操作简单、可重复性强。 OBJECTIVE: To establish a new animal model of early degeneration of rabbit lumbar intervertebral disc by means of non-invasive axial loading in upright position. Methods: Twenty-four male New Zealand white rabbits aged 4 months were randomly divided into experimental group and control group. The experimental animals were placed in a special tube so as to maintain the upright position, and imposed from the neck 600g axial load, 6h daily; control animals without any treatment and routine feeding. All animals were examined by X-ray and MRI before the start of the experiment and at 4, 8 and 12 weeks after the start of the experiment. The bony structure of the lumbar vertebra was observed in the experimental group. The disc height index DHI). The height of L2 / 3, L4 / 5 and L6 / 7 segments of intervertebral space were compared between the two groups. The relative gray value of nucleus pulposus was used to compare the change of water content of nucleus pulposus in both groups. After 14 weeks, all the animals were sacrificed and the nucleus pulposus of L5 / 6 segmental jelly was taken. The expression of collagen type I, type II collagen and proteoglycan were detected by rtPCR. The L6 / 7 segment disc and the upper and lower 1mm cartilage Under the bones, HE and Sirius red staining were used to observe the changes of disc tissue structure in each group. Results: Two experimental animals died during the experiment, and the corresponding experimental data were excluded from the results. Lumbar X-ray showed that under the condition of upright position weight, the lumbar formation of the experimental group was significantly kyphosis, significantly lower than that of the lumbar intervertebral space. In the L2 / 3 segment, the height of the intervertebral space was (P <0.05), 54.8% (P <0.05) in L4 / 5 and 47.9% (P <0.05) in L6 / 7. DHI measurements showed no significant difference in DHI between the two groups (P> 0.05) at any time point. MRI results showed that there was no significant difference in grayscale value of nucleus pulposus between the experimental group and the control group at any time point in L2 / 3 segment (P> 0.05). In L4 / 5 segment, nucleus pulposus of experimental group and control group There was a significant difference (P <0.05) between relative gray value at 12 weeks and at 8th week in L6 / 7 (P <0.05). The results of rt-PCR showed that the mRNA expression of type I collagen in experimental group was significantly higher than that in control group (3.57-fold, P <0.05), while the expression of type II collagen and proteoglycan was significantly lower than those in control group (0.35- and 0.43- P <0.05). Pathological examination showed that the structure of the intervertebral disc between the control group and the experimental group was significantly different. The boundary between the nucleus pulposus and the annulus fibrosus in the control group was clear. The nucleus pulposus was rich in uniformly distributed nucleus pulposus cells. The nucleus pulposus area is correspondingly reduced. CONCLUSION: Non-invasive axial loading of upright posture can significantly accelerate the degeneration process of rabbit lumbar intervertebral disc, which is more similar to human disc degeneration in pathogenesis. The animal model of lumbar disc degeneration is simple and reproducible.