基质金属蛋白酶-9的表达变化与实验性家兔脊髓空洞前状态的关系

Relationship between expression of MMP-9 and presyrinx state of experimental syringomyelia of rabbits

目的 探讨家兔脊髓空洞症模型脊髓基质金属蛋白酶（MMP）-9的表达变化与脊髓空洞前状态中脊髓水肿形成的关系,评价强力霉素对脊髓空洞前状态水肿形成的抑制作用.方法 中国白兔96只,随机分为4组：Kaolin组、强力霉素组、生理盐水组、假手术组各24只.家兔在麻醉后,行经皮枕大池穿刺术,Kaolin组和强力霉素组动物注入37 ℃ 25%Kaolin悬浊液0.6 ml 依同样方法生理盐水组动物仅注入37℃生理盐水0.6 ml 强力霉素组动物给予强力霉素25 mg·kg-1·d-1胃管内注入,持续14 d 假手术组只做枕大池假穿刺术,既不注射Kaolin也不注入生理盐水.在第1、3、7、14天,各时间点随机抽取Kaolin组、强力霉素组、生理盐水组、假手术组动物各6只处死后,取出颈髓,应用干湿法测定脊髓空洞前状态中脊髓含水量,应用免疫印迹和免疫组织化学方法测定脊髓中MMP-9表达含量.结果 各时间点Kaolin组动物颈髓组织中MMP-9表达和脊髓含水量与生理盐水组和假手术组相比明显增高（P＜0.01） 强力霉素治疗组与Kaolin组相比第1天差异无统计学意义（P＞0.05） 余各时间点动物脊髓含水量及颈髓组织中MMP-9表达与Kaolin组比较有明显降低（P＜0.01）.结论 在实验性家兔脊髓空洞症模型中,脊髓MMP-9高表达在脊髓空洞前状态水肿形成中起重要作用,强力霉素具有临床应用治疗脊髓空洞前状态的可能性.

Objective To investigate the relationship between the expression of MMP-9 and the formation of spinal cord edema in presyrinx state of experimental syringomyelia in rabbits and evaluate the inhibitory function of doxycline in the formation of spinal cord edema in presyrinx state. Methods A total of 96 Chinese white rabbits were divided randomly into four groups：kaolin group （n =24）, doxycline treatment group （n = 24 ）, physiological saline group （ n = 24 ） and control group （ n = 24 ） . Under ketamine anesthesia, 0. 6 ml of 25% kaolin solution was injected into the cisterna magna in all rabbits of kaolin and doxycline groups while 0. 6 ml of 37 ℃ physiological saline into the cistern in those of saline group doxycline （25 mg· kg-1 · d-1 ） was applied post-operatively for doxycline group. At Days 1, 3, 7 and 14 after kaolin injection, 6 rabbits of all four groups were selected randomly for sacrificing. Water content of spinal cord could be obtained. The expression of MMP-9 activity was measured by Western blot and imumunohistochemistry. Results At any time point, the water content of spinal cord and the expression of MMP-9 in kaolin group improved obviously more than those of saline and control groups（P 〈0. 01 ）. At Day 1, there was no marked difference in the water content of spinal cord and the expression of MMP-9 between doxycline and kaolin groups （ P 〉 0. 05 ）. At other time pionts, the water content of spinal cord and the expression of MMP-9 in doxycline group markedly decreased than those of kaolin group （P〈0. 01）.Conclusion In the model of experimental syringomyelia, MMP-9 plays an important role in causing edema in presyrinx state. Thus doxycline may be used to prevent and treat syringomyelia.