慢性压迫性脊髓症基质金属蛋白酶-9表达与血脊髓屏障破坏的相关性研究

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目的 观察慢性压迫性脊髓症大鼠模型脊髓基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达和血脊髓屏障(blood spinal cord barrier,BSCB)的变化,探讨二者相关性.方法 将48只成年SD大鼠随机分为假手术组和脊髓压迫组,每组各24只;将吸水后可膨胀聚氨酯薄板植入C5椎板下硬膜外,建立慢性压迫性脊髓症模型.造模后第4周,两组分别通过BBB(Basso Beattie Bresnahan)评分和体感诱发电位(somatosensory evoked potential,SEP)检测评价脊髓功能,每组各取12只行MMP-9、内皮屏障抗原(endothelial barrier antigen,EBA)免疫组化染色、检测二者在脊髓不同区域表达情况;其余12只行伊文思蓝(evans blue,EB)灌注检测BSCB通透性.统计学方法比较两组各观察指标差异,并分析脊髓压迫组MMP-9与EBA表达变化的相关性.结果 成功造模后第4周脊髓压迫组BBB评分显著低于假手术组;相对于假手术组,脊髓压迫组SEP检测潜伏期显著延长、波幅显著降低.脊髓压迫组白、灰质MMP-9表达均显著高于假手术组,脊髓压迫组灰质EBA表达显著低于假手术组,白质EBA表达无显著变化,脊髓压迫组EB含量显著高于假手术组;脊髓压迫组MMP-9表达与EBA表达半定量结果进行配对样本相关性分析显示两者呈显著相关(r=0.96,P=0.000).结论 慢性压迫性脊髓症大鼠模型建立第4周,脊髓功能显著降低,同时BSCB结构破坏、通透性增加,MMP-9表达增强并与EBA抗原显著减少显著相关,提示BSCB破坏可能与MMP-9表达显著增高相关.“,”Objective To investigate the correlation between the expression of MMP-9 and the disruption of the blood spinal cord barrier (BSCB) in chronic cervical cord compressive myelopathy rat model.Methods 48 adult rats were randomly divided into group A (sham surgical group,n=24) and group B (spinal cord compressive group,n=24).A water-absorbing polymer sheet was implanted into the C5 epidural space on the posterolateral side to induce a chronic spinal cord compression model.BBB scores and SEP were collected 4 weeks after surgery.Expression of MMP-9 and endothelial barrier antigen (EBA) were detected immunohistochemically in different spinal cord areas of 12 rats in each group.The other 12 rats were performed with Evans blue (EB) perfusion to observe the permeability of BSCB.The results and the correlation between MMP-9 and EBA expression were analyzed.Results BBB score was lower in spinal cord compressive group than that of sham surgical group.Latency was delayed and amplitude was reduced significantly in spinal cord compressive group.Expression level of MMP-9 in spinal cord compressive group was significant higher than that in both grey matter and white matter in sham surgical group.In the contrary,EBA expression was obviously more in grey matter of sham surgical group than that in spinal cord compressive group,while it showed no significant change in white matter between the 2 groups.EB perfusion in sham surgical group was less than that in spinal cord compressive group.MMP-9 expression was correlated with EBA staining significantly.Conclusion Neurological function of spinal cord in the compression group was abnormal,with a marked decline 4 weeks after model made.The increased permeability and structural failure of BSCB in chronic spinal cord compression myelopathy,which was characterized and correlated with increment of MMP-9 expression and decrement of EBA expression concurrently.Disruption of BSCB may be correlated with distinct increasing expression of MMP-9.
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