晚期骨关节炎患者血清和关节液中基质金属蛋白酶-13和肿瘤坏死因子-α水平的变化及其意义

摘要

目的 比较两级骨关节炎血清与关节液中基质金属蛋白酶-13(MMP-13)和肿瘤坏死因子-α (TNF-α)的水平,探讨其与膝骨关节炎WOMAC指数之间的相关性.方法 选取2015年9月至2016年 4月,我院收治的42例3级与4级膝骨关节炎患者(平均年龄64±8.8岁)作为研究对象,所有患者均行全膝关节置换术.采用酶联免疫吸附法测量患者术前静脉血和术中膝关节液中TNF-α 与MMP-13水平.对患者术前及术后1个月的膝关节功能进行WOMAC指数评估.结果 患者的血清TNF-α 水平(0.226±0.246)pg/ml 显著高于关节液(0.124±1.59)pg/ml(P<0.05),关节液MMP-13水平(4.31±1.24)pg/ml显著高于血清 (1.089±1.519)pg/ml(P<0.05).4级膝骨关节炎患者的关节液MMP-13水平(5.76±4.82)pg/ml显著高于 3级膝骨关节炎患者(2.95±2.45)pg/ml(P<0.05),而3级膝骨关节炎患者的血清MMP-13水平(1.128±0.308)pg/ml与4级膝骨关节炎患者(1.038±0.204)pg/ml相比,差异无统计学意义(P>0.05).4级膝骨关节炎患者的血清TNF-α 水平(0.293±0.140)pg/ml显著高于3级膝骨关节炎患者(0.204±0.109)pg/ml差异有统计学意义(P<0.05),而3级膝骨关节炎患者关节液TNF-α 水平(0.129±0.052)pg/ml与4级膝骨关节炎患者(0.118±0.014)pg/ml相比,差异无统计学意义(P>0.05).关节液MMP-13水平与术后WOMAC评分呈正相关(P<0.05).结论 随着骨关节炎等级的增高,TNF-α 的全身水平会不断升高;而MMP-13水平的升高只发生在局部病灶,且与患者的术后WOMAC评分呈显著相关.%Objective To compare serum and synovial fluid levels of matrix metalloproteinase-13 ( MMP-13 ) and tumor necrosis factor-alpha ( TNF-α ) in 2 stages of osteoarthritis, and to investigate their correlation with Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) scores. Methods Forty-two patients ( mean age: 64 ± 8.8 years ) with grade 3 or grade 4 knee osteoarthritis according to Kellgren-Lawrence criteria in our hospital from September 2015 to April 2016 were enrolled in the study and underwent total knee arthroplasty. TNF-α and MMP-13 levels were measured preoperatively from venous blood samples and intraoperatively from knee synovial fluid via enzyme-linked immunosorbent assay. Preoperative and 1-month postoperative knee functions were assessed by WOMAC. Results Mean serum TNF-α ( 0.226 ± 0.246 ) pg / ml was elevated compared to synovial levels ( 0.124 ± 1.59 ) pg / ml ( P < 0.05 ) and synovial MMP-13 ( 4.31 ± 1.24 ) pg / ml was elevated compared to serum levels ( 1.089 ± 1.519 ) pg / ml ( P < 0.05 ). Grade 4 synovial fluid MMP-13 ( 5.76 ± 4.82 ) pg / ml was significantly elevated compared to grade 3 ( 2.95 ± 2.45 ) pg / ml ( P < 0.05 ), whereas there was no significant difference in serum MMP-13 between grade 3 ( 1.128 ± 0.308 ) pg / ml and grade 4 ( 1.038 ± 0.204 ) pg / ml ( P > 0.05 ). Grade 4 serum TNF-α ( 0.293 ± 0.140 ) pg / ml was significantly elevated compared to grade 3 ( 0.204 ± 0.109 ) pg / ml ( P < 0.05 ), whereas there was no significant difference in synovial fluid TNF-α between grade 3 ( 0.129 ± 0.052 ) pg / ml and grade 4 ( 0.118 ± 0.014 ) pg / ml. Positive correlation was observed between synovial fluid MMP-13 levels and postoperative WOMAC scores ( P < 0.05 ). Conclusions Despite the systemic increase in TNF-α levels concordant with osteoarthritis grade, MMP-13 levels are elevated via local manner, with a significant correlation with WOMAC scores.