两种肿瘤坏死因子抑制剂对强直性脊柱炎患者血清金属蛋白酶-3浓度的影响

目的 探讨强直性脊柱炎（AS）患者经两种肿瘤坏死因子抑制剂治疗后,其血清基质金属蛋白酶（MMP）-3浓度的变化.方法 用人鼠嵌合的抗肿瘤坏死因子单克隆抗体Infliximab（英利昔单抗）和重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白Etanercept（依那西普）分别治疗了47例和26例活动期AS患者,在治疗前和治疗后不同时间点分别留取外周血清,应用酶联免疫吸附试验（ELISA）检测不同时间点血清中MMP-3的浓度,并与临床参数进行统计学分析.结果 Infliximab治疗AS患者6周后,与治疗前的基线期相比,血清MMP-3的水平在第2、6、10周均显著下降（P＜0.01）;在第2、6和10周,MMP-3水平与血红细胞沉降率（ESR）之间呈显著相关性（P＜0.05）.Etanercept治疗AS患者12周后,与治疗前相比,血清MMP-3的水平在第1、2、4、8和12周均显著下降（均P＜0.01）;在治疗前（0周）MMP-3的浓度与ESR（r=0.74,P＜0.01）、C-反应蛋白CRP（r=0.72,P＜0.01）之间均呈显著相关性;在治疗结束（12周）时,MMP-3的浓度与ESR之间也具有显著相关性（r=0.43,P=0.029）,与CRP之间的相关性未达到显著性（r=0.37,P=0.061）.结论 Infliximab和Etanercept不仅能显著降低通常用于评价病情活动的客观指标ESR和CRP,而且还能显著降低AS外周血清中MMP-3的浓度.MMP-3与AS的发病和病情活动有关,MMP-3有可能与ESR和CRP一样作为评价AS病情活动和评价抗肿瘤坏死因子抑制剂治疗AS疗效的一个有用的客观指标.

Effects of infliximab and etanercept, two types of anti-tumor necrosis factor-alpha inhibitor on serum level of matrix metalloproteinase 3 expression in patients with ankylosing spondylitis

OBJECTIVE: To evaluate the effect of Infliximab and Etanercept two types of anti-tumor necrosis factor-alpha (TNF-alpha) inhibitors, on the serum level of matrix metalloproteinase 3 (MMP-3) in the pathogenesis of ankylosing spondylitis (AS). METHOD: 47 patients with AS, 40 males and 7 females, aged 17 - 51, were treated with Infliximab (5 mg/kg i.v at weeks 0, 2, and 6); and 26 patients with AS were treated with Etanercept (25 mg, twice a week for 12 weeks). Clinical data including Bath AS indices (BASDAI and BASFI) and sera were collected at baseline and other different times. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. Serum levels of MMP-3 were measured with MMP-3 ELISA kits. RESULTS: Two, six, and ten weeks after Infliximab treatment the levels of ESR, CRP, and serum MMP-3 of the AS patients were all significantly lower than the baseline level (all P < 0.01), and the serum MMP-3 levels were all significantly correlated with ESR (all P < 0.05). In the Etanercept group 1, 2, 4, 8, and 12 weeks after treatment the levels of serum MMP-3, ESR, CRP, BASDAI, and BASFI were all significantly lower than the baseline levels (all P < 0.01); before the treatment ESR was significantly correlated with CRP (r = 0.80, P < 0.01), BASDAI was significantly correlated with BASFI (r = 0.48, P < 0.05), and MMP-3 was significantly correlated with ESR (r = 0.74, P < 0.01) and with CRP (r = 0.72, P < 0.01); and 12 weeks after the treatment significant correlation still existed between ESR and CRP (r = 0.40, P < 0.05), BASDAI and BASFI (r = 0.89, P < 0.01), and MMP-3 and ESR (r = 0.43, P = 0.029), however, there was no significant correlation between CRP and serum level of MMP-3 (r = 0.37, P = 0.061). CONCLUSION: Infliximab and Etanercept, 2 anti-TNF-alpha inhibitors, not only significantly decrease the ESR and CRP, but also decrease the serum level of MMP-3 of patients with AS. MMP-3 is involved in the pathogenesis and disease activity of AS. MMP-3 is also a potentially useful marker of AS disease activity and useful parameter to assess the effectiveness of anti-TNF-alpha inhibitor in treatment of AS.