基质金属蛋白酶-3在评价Etanercept治疗强直性脊柱炎疗效中的价值

Serum metalloproteinase-3 levels in assessing efficacy of Etanercept in patients with ankylosing spondylitis

目的:通过检测强直性脊柱炎(AS)患者血清和关节液,以及Etanercept治疗前后基质金属蛋白酶-3(MMP-3)浓度的变化,分析与AS疾病活动的相关性,探讨MMP-3在评价肿瘤坏死因子抑制剂治疗强直性脊柱炎疗效中的价值。方法:采用酶联免疫吸附试验(ELISA),检测48例AS患者在Etanercept治疗前0周,治疗后6周、12周的血清MMP-3浓度,同时对比检测30例健康志愿者外周血清标本和10例AS患者膝关节液中MMP-3水平。结果:48例AS患者血清MMP-3表达水平均明显高于正常对照组,AS患者膝关节液中MMP-3浓度也显著高于其血清中的浓度。有外周关节炎组AS患者的血清MMP-3浓度明显高于无关节炎组(P<0.001),而红细胞沉降率(ESR)与C反应蛋白(CRP)在两组比较中差异无统计学意义。AS患者在Etanercept治疗后第6周、第12周,血清MMP-3的表达水平明显下降(P<0.01),ESR和CRP,以及评价AS疾病的活动指数(BASDAI)和功能指数(BASFI),也均有下降趋势,并有统计学意义(均P<0.01)。在Etanercept治疗前(0周),血清MMP-3浓度与ESR、CRP、BASDAI、BASFI之间均具有显著相关性(P<0.05),ESR与CRP、BASFI亦有相关性,但与BASDAI的相关性无统计学意义(r=0.361,P=0.071)。在治疗12周后,血清MMP-3浓度仍与ESR、CRP、BASDAI呈很好的相关性(P<0.05),但与BASFI的相关性无统计学意义(P=0.339);ESR与CRP之间具有显著相关性,但与BASDAI、BASFI无统计学意义。BASDAI与BASFI有显著相关性(r=0.818,P=0.001)。结论:MMP-3可以作为评价AS患者病情活动性的客观指标,并且有可能比常规评价指标如ESR和CRP具有更强相关性。MMP-3也可以检测Etanercept治疗AS患者后的疗效,有可能成为客观评价昂贵生物制剂疗效的指标之一。

Objective： To investigate the value of metalloproteinase-3（MMP-3） levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis（AS）.Methods： The serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay（ELISA） in 48 patients with AS in week 0,6 and 12;and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls.Results： The serum levels of MMP-3 in AS patients were significantly higher than those in controls.In AS patients,the MMP-3 levels in synovial fluid were significantly higher than those in serum levels.The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement;while C-reactive protein（CRP） levels and erythrocyte sedimentation rate（ESR） did not differ between these 2 groups of AS.At week 6 and week 12 of etanercept treatment,the serum MMP-3 levels were significantly decreased（p0.01） with the declining trend of ESR,CRP,Bath Ankylosing Spondylitis Disease Activity Index（BASDAI） and Bath Ankylosing Spondylitis Functional Index（BASFI）（all p0.01）.Before the etanercept treatment（week 0）,serum levels of MMP-3 were correlated with ESR,CRP,BASDAI and BASFI（p0.05）.ESR was also correlated with CRP and BASFI,but not with BASDAI（r=0.361,P=0.071）.At weeks 12,serum MMP-3 levels were still correlated with ESR,CRP and BASDAI（P0.05）,but not with BASFI（P=0.339）;ESR was correlated with CRP,but not with BASDAI and BASFI.There was a significant correlation between BASDAI and BASFI（r=0.818,P=0.001）.Conclusion： Serum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.