英夫利昔单抗治疗强直性脊柱炎的疗效及对miR-146a表达的影响

Effect of infliximab on ankylosing spondylitis and its influence on miR-146a

目的探讨强直性脊柱炎(ankylosing spondylitis,AS)患者应用英夫利昔单抗治疗的效果及其对miR-146a表达的影响。方法 AS患者70例随机分为观察组和对照组各35例,对照组给予常规治疗,观察组在对照组基础上给予英夫利昔单抗治疗。治疗12周后评价2组近期疗效,记录不良反应发生情况;分别于治疗前、治疗后评定2组强直性脊柱炎病情活动性指数(Bath Ankylosing Spondylitis Disease Activity Index,BASDAI)、胸廓扩张度、脊柱活动度、脊柱疼痛视觉模拟评分(visual analogue scale,VAS),记录晨僵时间,检测血清红细胞沉降率(erythrocyte sedimentation rate,ESR)、C反应蛋白(C-reactive protein,CRP)、DKK-1水平及miR-146a表达。结果观察组BASDAI50(77.14%)、ASAS20患者比率(80.00%)均高于对照组(8.57%、17.14%)(P<0.05);观察组不良反应发生率(17.16%)与对照组(11.44%)比较差异无统计学意义(P>0.05);观察组治疗后BASDAI评分(2.1±0.9),脊柱疼痛VAS评分(3.6±0.3),血清ESR[(10.33±1.75)mm/h]、CRP[(4.58±1.02)mg/L]及DKK-1[(332.18±20.33)ng/L]较治疗前降低[5.9±1.3、7.5±1.1、(68.41±9.90)mm/h、(24.49±4.10)mg/L、(409.32±28.50)ng/L]、胸廓扩张度[(5.2±2.9)cm]、脊柱活动度[(5.5±1.5)cm]较治疗前[(3.1±1.2)、(3.6±0.8)cm]增加,晨僵时间[(11.9±4.4)min]较治疗前[(31.7±5.9)min]缩短(P<0.05);对照组治疗后BASDAI评分(4.6±1.3),脊柱疼痛VAS评分(5.4±1.4),血清ESR[(44.12±4.99)mm/h]、CRP[(17.47±4.20)mg/L]较治疗前[5.8±1.2、7.4±1.0、(69.55±10.48)mm/h、(23.31±4.45)mg/L]降低,脊柱活动度[(4.1±1.3)cm]较治疗前[(3.2±1.0)cm]增加,晨僵时间[(20.2±5.1)min]较治疗前[(33.3±6.8)min]缩短(P<0.05);观察组各指标改善优于对照组(P<0.05);观察组、对照组治疗后miR-146a表达(0.78±0.23、1.44±0.42)低于治疗前(2.02±0.77、2.11±1.20)(P<0.05),且观察组治疗后miR-146a表达低于对照组(P<0.05)。结论 AS患者应用英夫利昔单抗治疗近期疗效满意,安全性良好,其机制可能与降低miR-146a表达、诱导缓解病情有关。

Objective To investigate the effect of infliximab on ankylosing spondylitis（AS）and its influence on the expression of miR-146 a.Methods Seventy patients with AS were randomly divided into observation group and control group,with 35 patients in each group.Control group was given conventional treatment,while observation group was given infliximab therapy besides the therapy in control group.After 12-week treatment,the short-term effect was evaluated and the incidence of adverse reactions was recorded in two groups.Bath Ankylosing Spondylitis Disease Activity Index（BASDAI）,thoracic expansion,spinal mobility,spinal visual analogue scale（VAS）and morning stiffness duration were recorded,and the levels of serum erythrocyte sedimentation rate（ESR）,C-reactive protein（CRP）,Dickkopf-1（DKK-1）and miR-146 a were detected before and after treatment between two groups.Results The proportions of BASDAI50 patients and ASAS20 were significantly higher in observation group（77.14%,80.00%）than those in control group（8.57%,17.14%）（P〈0.05）.There was no significant difference in the incidence of adverse reactions between observation group（17.16%）and control group（11.44%）（P〈0.05）.BASDAI score,spinal VAS score,serum ESR,CRP and DKK-1 were significantly lower in observation group after treatment（2.1±0.9,3.6±0.3,（10.33±1.75）mm/h,（4.58±1.02）mg/L,（332.18±20.33）ng/L）than those before treatment（5.9±1.3,7.5±1.1,（68.41±9.90）mm/h,（24.49±4.10）mg/L,（409.32±28.50）ng/L）（P〈0.05）,the degree of thoracic expansion and spinal activity were significantly larger after treatment（（5.2±2.9）,（5.5±1.5）cm）than those before treatment（（3.1±1.2）,（3.6±0.8）cm）,and morning stiffness duration was significantly shorter than before treatment（（11.9±4.4）min vs（31.7±5.9）min）（P〈0.05）.The BASDAI,spinal VAS score,and levels of serum ESR and CRP were significantly lower in control group after treatment（4.6±1.3,5.4±1.4,（44.12±4.99）mm/h,（17.47±4.20）mg/L）than those before treatment（5.8±1.2,7.4±1.0,（69.55±10.48）mm/h,（23.31±4.45）mg/L）,the spinal activity was significantly larger after treatment（（4.1±1.3）cm）than that before treatment（（3.2±1.0）cm）,and morning stiffness duration was significantly shorter than that before treatment（（20.2±5.1）min vs（33.3±6.8）min）（P〈0.05）.The improvement of all above indexes was more significantly obvious in observation group than in control group（P〈0.05）.The expressions of miR-146 ain observation group and control group were significantly lower after treatment（0.78±0.23,1.44±0.42）than those before treatment（2.02±0.77,2.11±1.20）（P〈0.05）,and lower in observation group than in control group after treatment（P〈0.05）.ConclusionInfliximab is effective and safe for AS,probably by reducing the expression of miR-146 aand relieving AS.