Upright posture combined with noninvasive axial loading-induced rabbit intervertebral disc degeneration

English Keywords:Intervertebral disc degeneration  Animal model  Axial load  Noninvasive  Rabbit

English Abstract:

  【Abstract】 Objectives: To establish a novel in vivo rabbit model of early intervertebral disc degeneration(IDD) that can better simulate the IDD process in humans. Methods: 24 four-month-old male New Zealand white rabbits were randomly assigned into two groups(experimental group and control group). Each rabbit in the experimental group(n=12) was placed into a plastic tube specially designed to maintain the animal in an upright posture. A collar weighed 600g was placed onto the neck of each experimental rabbit, 6 hours for one day. Rabbits in the control group(n=12) were regularly fed in their cages throughout the experiment. Before the experiment and at 4, 8 and 12 weeks after the experiment, lumbar lateral radiographs and MRI were taken in the lateral decubitus position for both the experimental group and the control group to monitor the signs of disc degeneration by measuring disc height index(DHI) and grayscale values of nucleus pulposus(NP). At 14 weeks, all animals in both groups were sacrificed. The NPs of L5/6 were obtained for quantitative real time-PCR(rt-PCR) analysis. Disc segment L6/7 was obtained for histologic analysis. The specimens were cut midsagittally and stained with hematoxylin and eosin(H&E) and picrosirius red. Results: Two rabbits in the experimental group died during the study, and their data were not included in the final results. The lateral radiograph of rabbits in the experimental group which had been placed into the tube and maintained in an upright position showed that there was an obvious kyphotic curvature on the lower lumbar spine, and the disc height of L2/3, L4/5 and L6/7 was much smaller than the height in the image of the same rabbit in lateral decubitus position, 75.1%, 54.8% and 47.9% respectively for each segment(all P<0.05). DHI measurement showed no significant difference between two groups at any time point. Serial MRI scans showed that animals in the experimental group presented a progressive decrease in the signal intensity of their lumbar discs over the 14-week period. In contrast, NP signal intensities in the control group decreased more slowly during the same period. Significant differences between two groups were observed since 12 weeks in L4/5(P<0.05) and 8 weeks in L6/7(P<0.05). The result of rt-PCR showed that the collagen type Ⅰ mRNA expressions were significantly greater(3.06-fold), whereas collagen type Ⅱ and aggrecan mRNA expressions were significantly less(0.35-fold and 0.37-fold respectively) in the experimental group than those in the control group(all P<0.05). Histologic examination showed significant difference between the control and experimental group. In the experimental group, there was a large increase in fibrocartilage lamellas in the inner border of posterior AF, resulting in a significantly decreased gelatinous NP area. Conclusions: The upright posture combined with noninvasive external loading method can induce accelerated degenerative changes in rabbit lumbar discs. These mild degenerative changes closely resemble those which occur in the early phase of disc degeneration in humans, which suggest its use in future studies.