腰椎间盘退变动物模型的建立

Animal model of intervertebral disk degeneration caused by bilateral zygapophysial joints destruction

目的制备椎间盘退变动物模型。方法将48只新西兰大白兔随机分为骨性手术组和软组织手术组。骨性手术组L4L5、L5L6为实验组椎间盘，L3L4、L6L7为自身对照组；软组织手术组L4L5、L5L6为实验对照组椎间盘。术后1、2、4及8个月行MRI及分子生物学检查。结果（1）MRI：兔髓核位于椎间盘中央，占椎间盘横截面积50％左右。术后1、2、4及8个月，3组椎间盘横断面T2高信号区域面积分数均逐渐减小（F=96．2～1544．4，P〈0．01）；术后相同时间段，实验组面积分数最小，自身对照组次之，实验对照组最高，差异有统计学意义（F=125．7～1850．6，P〈0．01）。（2）分子生物学：蛋白多糖、胶原为椎间盘主要细胞外基质，术后1、2、4及8个月，3组椎间盘蛋白多糖、Ⅱ型胶原表达量进行性下降（F=148．2～1544．4，P〈0．01），Ⅰ型胶原表达量进行性上升（F=94．3—579．6，P〈0．01）。术后相同时间段，实验组蛋白多糖、Ⅱ型胶原最小，自身对照组次之，实验对照组最高（F=135．5～3520．6，P〈0．01）；Ⅰ型胶原表达量实验组高于实验对照组、自身对照组（F=7．8—143．1，P〈0．01）。结论破坏关节突关节成功制备出椎间盘退变动物模型。

Objective To establish animal models of intervertebral disk degeneration caused by destroying bilateral zygapophysial joints of New-Zealand rabbits. Methods Forty-eight male New-Zealand rabbits were randomly divided into operation group on the bone and operation group on the soft tissue. In operation group on the bone, L4 and L5 inferior articular processes were en bloc excised,while L5 and L6 superior articular processes were retained. In the operation group on the soft-tissue, only L3 to L7 paravertebral muscles were stripped. In operation group on the bone, L4L5 and L5L6 intervertebral disks acted as experimental group, and L3L4 and L6L7 acted as self-control group. In the operation on the soft tissue, L4L5 and LSL6 acted as experiment-control group. One ,2,4 and 8 months post-operation, magnetic resonance imaging （MRI） and molecular biologic examination of intervertebral disks of New-Zealand rabbits were performed. Results （ 1 ） MRI ： On the T2-weighted midsagittal plane images, the nucleus pulposus was uniform high signal intensity. On the axial plane images, T2-weightcd high signal area fraction of the nucleus pulposus was 50%. One,2,4 and 8 months post-operation,MRI showed the most significantly decreased axial T2-weighted high-signal area fraction in the experimental group, and the smallest declined in the experiment-control group （F =94.3-579.6 ,P 〈0.01 ）. At the same time,the axial T2-weighted high-signal area fraction was the least in experiment group, whereas most in the experiment-control group （ F = 125.7-1850.6, P 〈 0.01 ）. （2） Molecular biologic examination：The main extracellular matrix of intervertebral disc included aggrecan, collagen type Ⅱ and collagen type Ⅰ. One,2,4 and 8 months post-operation, aggrecan and collagen type Ⅱ mRNA levels were decreased markedly （ F = 148.2-1544.4 ,P 〈 0.01 ） , whereas type Ⅰ collagen mRNA gradually increased （ F = 94.6-822.0, P 〈 0.01 ）. At the same time, aggrecan and collagen type Ⅱ gene expression was the least in experiment group, whereas most in the experiment-control group （ F = 135.5-3520.6 ,P 〈 0.01 ）. Collagen type Ⅰ showed the contra-tendency （ F = 7.8- 143.1, P 〈 0.01 ）. Conclusion By destroying L4L5 and L5L6 zygapophysial joints of adult rabbits, animal model of intervertebral disc degeneration was successfully established.