目的 了解RA患者中微RNA(miRNA)的表达情况及与临床表现、实验室检查、病情活动性、细胞因子水平以及治疗反应的相关性.方法 选取2015年10月至12月就诊于内蒙古医科大学附属医院风湿免疫科的初诊RA患者38例,实时荧光定量PCR检测38例初诊RA患者基线期、38名健康对照组及治疗后3个月RA患者PBMCs中miRNA表达量.计数资料采用χ2检验或Fisher确切概率法.计量资料采用独立样本t检验或配对t检验.Levene法检验方差齐性.结果 ①基线期RA患者组miR-125b(1.55±0.24),miR-155(3.1±0.5),miR-346(650±51),miR-223-3p(1.26±0.18),miR-146a-5p(2.39±0.25)表达高于健康对照组(0.84±0.16,1.4±0.5,304±101,0.58±0.11,1.09±0.27,t=15.36,18.60,18.77,19.67,21.66;P<0.05),miR-21-5p(0.91±0.09)表达低于健康对照组(1.52±0.21,t=-16.029,P<0.05),而miR-146a-3p,miR-21-3p,miR-223-5p表达在2组间差异并无统计学意义.②miRNA表达水平与RA临床表现、实验室检查、病情活动性和细胞因子包括IL-1β,IL-6,IL-17a,IL-23和TNF-α水平相关性进行相关性分析,发现miR-146a、miR-155的表达水平与RA病情活动度评分呈正相关(与DAS28、CDAS、SDAS评分的Pearson相关系数分别为0.877,0.877,0.877;0.817,0.817,0.817;P均<0.05);miR-21与RA病情活动度评分、炎性细胞因子呈负相关.③治疗后RA患者关节压痛、肿胀等临床症状、实验室指标及超声影像学检查均改善(P<0.05),RA患者miRNA的表达均减低(P<0.05),而miR-21表达则显著性增加(P<0.05).结论 MiR-125b,miR-21,miR-155,miR-346,miR-223,miR-146a在RA患者中差异化表达,且与病情活动和治疗反应相关,提示miRNA的检测可作为RA病情活动的判断指标,用于监测治疗效果.%Objective To investigate the correlation between miRNAs and clinical manifestations, laboratory examinations, serum cytokines and disease activity scores in rheumatoid arthritis (RA). Methods Thirty-eightnewly diagnosed RA patients who visited the department of Rheumatology of Inner Mongolia Medical Affiliated Hospital from October 2015 to December 2015 were enrolled in the study. Thirty-eight age and sex matched healthy volunteers were enrolled as the control group. MiR-125b, miR-21, miR-155, miR-346, miR-223, miR-146a were tested by real-time fluorescence quantitative polymerase chain reaction (real-time PCR). Datawere collected at the baseline and 3 weeks after the study. Solutions statistical package for the social sciences (SPSS) 20.0 version was usedfor statistical analysis. Data were analyzed using t test or χ2 test and Pearson test was used for correlation analysis.Levene method was used to test homogeneity of variance. Results MiR-125b (1.55±0.24), miR-155 (3.1±0.5), miR-346 (650±51), miR-223-3p (1.26±0.18), miR-146a-5p (2.39±0.25) levels in the RA group were significantly higher than those in the healthy control group at the baseline (0.84±0.16, 1.4±0.5, 304±101, 0.58±0.11, 1.09±0.27; t=15.36, 18.60, 18.77, 19.67, 21.66; P<0.05). MiR-21-5p (0.91±0.09) was lower than the control group (1.51±0.21; t=-16.029, P<0.05), while miR-146a-3p, miR-21-3p, miR-223-5p showed no difference between the two groups. MiR-155 and miR-146a was positively correlated with RA disease activity scores (P<0.05). MiR-21 was negatively correlated with disease activity scores and serum cytokines including IL-1β, IL-6, IL-17a, IL-23 and Tumor necrosis factor (TNF)-α. After 3 months treatment, tenderness joint count, swelling joint count, laboratory tests and imaging examination were improved (P<0.05), while miRNAslevels in RA were decreased significantly respectively (P<0.05), mir-21 was increased significantly. Conclusion MiR-125b, miR-21, miR-155, miR-346, miR-223, miR-146a in RA are characteristically expressed in RA and related with the disease activity and treatment response. MiRNAs may hold a great promise as the diagnostic and prognostic biomarkers in RA.
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