Topping-off技术防治椎间融合后邻近节段椎间盘退变实验研究

Effects of Coflex interspinous stabilization on the prevention of adjacent segment degeneration after spine fusion in dog models

目的探讨后路棘突间动态固定装置Coflex对比格犬腰椎间融合后相邻上位节段椎间盘退变的保护作用。方法选用16只健康成年比格犬,应用经皮穿刺比格犬腰椎间隙损伤椎间盘方法建立腰椎间盘退变动物模型,用配对比较法随机分为仅行椎间融合的对照组及行椎间融合加相邻节段Coflex置入(Toppingoff技术)的实验组,术后3、6个月行MRI检查、髓核组织II型胶原(COL-2)阳性细胞数及基质金属蛋白酶阻滞剂-1(TIMP-1)和骨形态发生蛋白-15(BMP-15)内参基因GAPDH含量测定。结果 MRI检查显示对照组与实验组犬腰椎间盘均有不同程度退变,实验组MRI T2图像半定量分析结果为2.92±0.21,对照组为1.69±0.11,实验组较对照组退变程度轻,差异有统计学意义(P<0.05);对照组术后6个月髓核的COL-2阳性细胞含量为8.66±1.31,较术后3个月时的12.33±1.24明显减少,差异有统计学意义(P<0.05);对照组术后6个月时TIMP-1、BMP-15基因表达量分别为1.86±0.14和1.98±0.24较术后3个月时的0.70±0.12和0.78±0.13明显上升,差异有统计学意义(P<0.05);实验组第3、6个月自身对照髓核的COL-2阳性细胞含量,TIMP-1、BMP-15基因表达量差异无统计学意义(P>0.05);实验组术后6个月髓核COL-2阳性细胞含量为11.33±1.74,明显高于对照组,差异有统计学意义(P<0.05),TIMP-1、BMP-15的基因表达量分别为0.85±0.13和0.98±0.14,明显低于对照组,差异有统计学意义(P<0.05)。结论后路棘突间固定装置Coflex对比格犬的腰椎间盘退变有一定保护作用,对椎间融合后相邻节段退变有一定延缓作用。

Objective Interspinous spacers（ ISPs） are promising in the treatment of adjacent segment degeneration（ ASD） after the spine fusion. Coflex is one of ISPs, however, its effectiveness evidence is still very limited. The purpose of this study is to further investigate the effects of Coflex in vivo after the spine fusion when implanted in beagle dogs. Methods The model of lumbar disc degeneration was established by percutaneous puncture of the intervertebral disc under the fluoroscopy. 16 healthy adult beagle dogs were randomly divided into the Control Group（ L6-7 intervertebral fusion） and Experiment Group（ L6-7 intervertebral fusion plus L5-6 interspinous process Coflex dynamic fixation） using paired comparison method. All were followed up for 6 months after the initial operation. Spine MRI images were evaluated at 3 and 6 months, respectively. Immunohistochemical and gene expression analyses were also performed at 3 and 6 months. Results Degeneration was observed in both Control and Experiment Group in MRI images. Outcomes of semi quantitative analysis of T2 images were（ 2.92 ± 0.21） and（ 1.69 ± 0.11） in the experiment and Control Group, respectively. The Control Group showed a more significant degeneration than the Experiment Group（ P 0.05）. The number of COL-2 positive cells decreased from（ 12.33 ± 1.24） 3 months postoperatively to（ 8.66 ± 0.14） 6 months postoperatively with statistical significance in the Control Group（ P 0.05）. Real-time PCR demonstrated that TIMP-1 and BMP-15 gene expressions increased from（ 0.70 ± 0.12）,（ 0.78 ± 0.13） 3 months postoperatively to（ 1.86 ± 0.14）,（ 1.98 ± 0.24） 6 months postoperatively with statistical significance（ P 0.05） in the Control Group. There were no significant differences in the number of COL-2 positive cells, TIMP-1 and BMP-15 expressions in the Experiment Group at 3 and 6 months（ P 0.05）. The number of COL-2 positive cells was（ 11.33 ± 1.74） in the Experiment Group at 6 months, which was significant more than that in the Control Group（ P 0.05）. TIMP-1 and BMP-15 gene expressions were（ 0.85 ± 0.13）,（ 0.98 ± 0.14） in the Experiment Group, which were significantly lower than that in the Control Group 6 months postoperatively（ P 0.05）. ConclusionsIntervertebral fusion could aggravate the degeneration of adjacent-segment intervertebral discs and Coflex could decelerate the progression of ASD after spine fusion.