骨关节炎患者关节镜清理术前后关节液中uPA、MMP-3、MMP-9、MMP-13和MMP-14表达水平的检测及其意义

摘要

目的：检测骨关节炎（OA）患者关节镜清理术前后关节液中尿激酶型纤溶酶原激活物（uPA）和基质金属蛋白酶（MMP）-3、MMP-9、MMP-13、MMP-14的表达水平，探讨关节清理手术对 uPA、MMP-3、MMP-9、MMP-13和 MMP-14表达的影响。方法：收集行关节镜诊治的膝 OA患者关节液标本420份，术后半年随访时获取关节液标本350份，对符合本实验条件的228份标本应用 ELISA法检测 uPA、MMP-3、MMP-9、MMP-13和 MMP-14的表达水平，比较术前术后 uPA、MMP-3、MMP-9、MMP-13和 MMP-14表达水平差异，采用Spearman相关分析探讨 uPA、MMP-3、MMP-9、MMP-13和 MMP-14与关节疼痛评分（VAS）之间的相关性。结果：所有患者均经临床随访6～70个月，平均随访时间36.5个月。与术前比较，术后半年时 OA患者关节液中 uPA和 MMP-3表达水平明显降低（P＜0.01）， MMP-9和 MMP-13略有下降（P＜0.05），而 MMP-14表达水平无明显变化（P＞0.05）；术前 uPA、MMP-3、MMP-9、MMP-13和 MMP-14表达水平与 VAS评分均呈正相关关系（r＝0.361、r＝0.417、r＝0.136、r＝0.514和r＝0.156，P＜0.05）；术后 uPA与 MMP-3表达水平呈正相关关系（r＝0.814，P＜0.05），uPA和 MMP-3表达水平与 VAS评分均呈正相关关系（r＝0.981、r＝0.831， P＜0.01），MMP-13表达水平与 VAS评分亦呈正相关关系（r＝0.145，P＜0.05），而 MMP-9和 MMP-14表达水平与 VAS评分无相关关系（P＞0.05）。结论：关节镜清理术能显著减轻患者关节疼痛症状，其作用机制可能与关节液中 uPA、MMP-3和 MMP-13表达水平下降有关。%Objective To detect the expression levels of urokinase-type plasminogen activator (uPA), matrix metalloproteinase-3 (MMP-3),MMP-9,MMP-13 and MMP-14 in the patients with osteoarthritis(OA)before and after arthroscopic debridement,and to explore the influence of arthroscopic debridement in the expressions of uPA, MMP-3,MMP-9,MMP-13, and MMP-14.Methods 420 cases of synovial fluid from knee OA patients undergoing arthroscopic debridement were obtained before operation. After six months follow-up, 350 cases of synovial fluid samples were obtained and according to inclusion and exclusion criteria, 228 synovial fluid were selected to analyze.The expression levels of uPA,MMP-3,MMP-9,MMP-13,and MMP-14 were measured by ELISA assay.Pain intensity of these patients before operation and six months after operation were recorded using the Visual Analogue Scale/Score(VAS).The differences of the expression levels of uPA,MMP-3,MMP-9, MMP-13,and MMP-14 between before operation and after operation were compared.The relationship between the expression levels of uPA, and MMP-3, MMP-9, MMP-13, MMP-14 and VAS was analyzed with Spearman analysis.Results All the patients were followed up for 36.5 months. Compared with before operation, the expression levels of uPA and MMP-3 in the synovial fluid of the patients after arthroscopic debridement were significantly decreased(P<0.01),the expression levels of MMP-9 and MMP-13 were also decreased (P<0.05), but the MMP-14 expression level showed no significant change.The expression levels of uPA,MMP-3,MMP-9, MMP-13,MMP-14 were positively associated with VAS before arthroscopic debridement (r=0.361,r=0.417, r=0.136,r=0.514,r=0.156,P<0.05 );uPA and MMP-3 were positively correlated with VAS after arthroscopic debridement(r=0.981,r=0.831,P<0.01),as well as the expression level of MMP-13 and VAS, but there were no significant differences between the expression levels of MMP-9, MMP-14 and VAS. Conclusion The decreased levels of uPA,MMP-3 and MMP-13 in synovial fluid may contribute to the pain-relief effects of arthroscopic debridement.