蛋白聚糖酶2与金属蛋白酶组织抑制剂3在腰椎间盘髓核退变中的表达及意义

Expression of matrix aggrecanase 2 and a tissue inhibitor of metailoproteinases in degenerated interverte- bral discs

目的观察人体腰椎间盘髓核在不同退变程度时蛋白聚糖酶2及金属蛋白酶组织抑制剂3（TIMP-3）的阳性表达，探讨其在髓核退变过程中的作用。方法选取脊柱外科腰椎手术摘除的髓核标本45例，采用Pfirrmann分级法对椎间盘髓核退变MRI进行分级。分为3组：对照组（Pfirrmann分级Ⅰ、Ⅱ级）、退变组（Pfirrmann分级Ⅲ-Ⅳ级）和严重退变组（Pfirrmann分级V级），每组15例。用4％多聚甲醛固定、石蜡包埋后，应用免疫组织化学方法检测髓核细胞中蛋白聚糖酶2及TIMP-3的表达。结果椎间盘髓核细胞中蛋白聚糖酶2的阳性细胞率在对照组、退变组、严重退变组分别为（13．58±7．76）％、（33．48±13．95）％、（56．00±18．39）％，且退变组与对照组比较，表达增强（P〈0．01）；严重退变组分别与对照组和退变组比较，表达均增强（P〈0．01）。对照组、退变组和严重退变组的TIMP-3阳性细胞率分别为（34．78±13．80）％、（46．77±10．98）％、（50．65±16．45）％，且退变组与对照组比较，表达增强（P〈0．05）；严重退变组与对照组比较，表达亦增强（P〈0．01）；严重退变组与退变组比较，表达也增强（P〈0．05）。对照组、退变组和严重退变组的蛋白聚糖酶2／TIMP-3比值分别为（45．37±30．57）％、（75．90±40．30）％和（120．62±49．67）％；退变组与对照组比较，比值升高（P〈0．05）；严重退变组分别与对照组和退变组比较，比值均升高（P〈0．01）。结论在腰椎间盘髓核中蛋白聚糖酶2与TIMP-3的表达及蛋白聚糖酶2／TIMP-3比值均随髓核退变程度加重而升高，提示二者与髓核退变有密切关系，其比值升高与髓核退变程度呈正相关。

Objective To observe the expression of aggrecanase 2 and a tissue inhibitor of metalloprotein- ase 3 （ TIMP-3 ） in degenerate human lumbar intervertebral discs and their role in degeneration of the nucleus pul- posus. Methods Pfirrmann classification was used to class degenerate intervertebral discs observed through MRI. They were divided into three groups： a control group （Pfirrmann grade I -II ） , a degeneration group （Pfir- rmann grade m -IV ） , and a severe degeneration group （ Pfirrmann grade V ）. A total of 45 cases accepted lumbar spine surgery for removing nucleus pulposus specimens. Each group contained 15 cases. After formalin-fixation and paraffin embedding, immunohistochemistry was used to detect aggrecanase 2 and TIMP-3 expression in the nucleus pulposus cells. Results The percentages of cells positive for aggreeanase 2 were （ 13.58± 7.76） % , （ 33.48 ± 13.95）% and （56.00 ± 18. 39 ）% in the control, degeneration and severe degeneration groups respectively. These differences had statistical significance. The percentages of cells positive for TIMP-3 were （34. 78± 13.80） % , （46.77± 10.98） % and （50.65±16.45） % , and these differences were again statistically signifi- cant. The aggreeanase 2/TIMP-3 ratios were also significantly different. Conclusion As the degree of degenera- tion of the nucleus pulposus increased, the expression of aggrecanase 2 and TIMP-3 rose, which indicates that both changes were closely connected with the degeneration. Their ratio was correlated with the degree of degeneration of the nucleus pulposus.