类风湿关节炎患者血清基质金属蛋白酶-9及细胞外基质金属蛋白酶诱导因子水平与颈动脉粥样硬化的相关性研究

The Association of Serum MMP-9,EMMPRIN and Carotid Atherosclerosisin Patients with Rheumatoid Arthritis

目的研究类风湿关节炎(RA)患者血清基质金属蛋白酶-9(MMP-9)及细胞外基质金属蛋白酶诱导因子(EMMPRIN)的变化,探讨其与RA发生颈动脉粥样硬化的相关性。方法通过高分辨超声检测颈动脉内中膜厚度(IMT)和有无动脉斑块形成,将75例RA患者分为合并颈动脉粥样硬化组(RA-AS组,44例)和非颈动脉粥样硬化组(RA-nonAS组,31例)和32例健康体检正常者(对照组)作为研究对象。采用ELISA法测定3组血清MMP-9和EMMPRIN水平,记录RA患者病程、体质指数(BMI)、类风湿关节炎疾病活动评分(DAS28)、类风湿因子(RF)、血脂、空腹血糖、糖化血红蛋白(GHbA1c)、血沉(ESR)、超敏C反应蛋白(hs-CRP)、胰岛素抵抗指数(HOMA-IR)等临床资料。Spearman相关性研究分析MMP-9与EMMPRIN的关系。用受试者工作特征曲线(ROC)及曲线下面积(AUC)评价血清MMP-9和EMMPRIN水平对RA合并颈动脉粥样硬化的诊断价值。采用Logisitic回归分析RA合并颈动脉粥样硬化的影响因素。结果RA-AS组患者血清MMP-9[47.25(27.52,66.36)ng/mL]与EMMPRIN[5.49(3.26,7.56)ng/mL]水平均显著高于RA-nonAS组[MMP-9:19.36(11.50,27.98)ng/mL,EMMPRIN:3.279(2.44,4.47)ng/mL],non-AS组MMP-9和EMMPRIN水平显著高于对照组[MMP-9:7.89(5.32,14.38)ng/mL,EMMPRIN:2.643(1.69,4.37)ng/mL];RA患者血清MMP-9水平与EMMPRIN水平呈正相关性(r=0.562,P<0.001);MMP-9预测RA患者合并颈动脉粥样硬化的ROC-AUC为0.805(95%CI:0.7024~0.9075);EMMPRIN预测RA患者合并颈动脉粥样硬化的ROC-AUC为0.729(95%CI:0.6163~0.8426)。Logistic回归分析显示年龄、病程、DAS28、hs-CRP与MMP-9是影响RA患者颈动脉粥样硬化的独立相关因素。结论RA患者血清MMP-9、EMMPRIN表达增加,RA疾病活动与患者颈动脉粥样硬化的发生密切相关,二者联合检测对动脉粥样硬化的早期诊断有一定临床意义。

Objective To investigate levels of serum matrixmetalloproteinase-9(MMP-9)and extracellular matrix metalloproteinase inducer(EMMPRIN)in patients with rheumatoid arthritis(RA),and to explore their relationships with carotid atherosclerosis.Methods According to carotid intima-media thickness(IMT)and atherosclerotic plaque via high-resolution ultrasonography,75 patients with RA were included and divided into the RA with carotid atherosclerosis group(RA-AS group,44 cases)and RA without carotid atherosclerosis group(RA-nonAS group,31 cases),while 32 healthy controls(control group)were also enrolled.ELISA was conducted to detect levels of serum MMP-9 and EMMPRIN for all subjects.Pathogenesis,disease activity score-28(DAS28),body mass index(BMI),lipid,fasting blood glucose(FBG),glycosylated hemoglobin(GHbA1c),homeostasis model assessment of insulin resistance(HOMA-IR),erythrocyte sedimentation rate(ESR)and high sensitivity C-reactive protein(hs-CRP)were also determined and recorded.Spearman analysis was applied to evaluate the relationship between MMP-9 and EMMPRIN in patients with RA.Receiver operating characteristic curves(ROC)were plotted,and area under the curve(ROC-AUC)was used to assess diagnostic value about serum MMP-9 and EMMPRIN in RA for carotid atherosclerosis.Logistic regression analysis was used to analyze the risk factors of RA complicated with carotid atherosclerosis.Results Both levels of serum MMP-9 and EMMPRIN in the RA-AS group[MMP-947.25(27.52,66.36)ng/mL,EMMPRIN 5.49(3.26,7.56)ng/mL]were significantly increased compared with the RA-nonAS group[MMP-919.36(11.50,27.98)ng/mL,EMMPRIN 7.89(5.32,14.38)ng/mL](P<0.05).Levels of serum MMP-9 and EMMPRIN were significantly increased in the RA-nonAS group compared with the control group[MMP-910.71(4.22,14.74)ng/mL,EMMPRIN 2.643(1.69,V4.37)ng/mL](P<0.01).Spearman correlation analysis indicated that serum MMP-9 was positively correlated with EMMPRIN in patients with RA(r=0.562,P<0.001).ROC-AUC of MMP-9 and EMMPRIN for the diagnosis of carotid AS in patients with RA were 0.805(95%CI:0.7024,0.9075)and 0.729(95%CI:0.6163,0.8426),respectively.Logistic regression analysis showed that age,pathogenesis,DAS-28 and MMP-9 were the independent risk factors for carotid atherosclerosis in patients with RA(all P<0.05).Conclusion The increased expression of serum MMP-9 and EMMPRIN along with disease activity are closely correlated with the incidence of carotid atherosclerosis in patients with RA.The combined detection of serum MMP-9 and EMMPRIN have promising predictive significance for the early detection of atherosclerosis in RA.