MiR-21在托法替布治疗中重度活动性类风湿性关节炎中的作用研究

The Research of the Role of MiR-21 in the Treatment of Moderate and Severe Active Rheumatoid Arthritis with Tofacitinib

摘要: 目的：探讨初发类风湿性关节炎(RA)患者应用托法替布前后患者外周血单个核细胞(PBMC)中miR-21、STAT3mRNA表达变化及其临床意义。方法：选择初发RA患者60例，健康体检者(HC) 40例。初发RA患者给予甲氨蝶呤(MTX)治疗3个月；3个月后单用MTX病情控制不佳的患者联合托法替布治疗，随访3个月。采用qRT-PCR法检测受试者服药前后PBMC中miR-21、STAT3mRNA表达。观察并记录两组试验研究对象实验室检查资料，包括血沉(ESR)、高敏C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(CCP)、并进行疾病活动活度评分(DAS28)。结果：初发RA患者PBMC中miR-21与健康人相比表达显著降低，而STAT3mRNA表达显著升高(p均 < 0.01)。与单用MTX相比，病情控制不佳加用托法替布后PBMC中miR-21表达升高，而STAT3mRNA表达降低(p均 < 0.01)。Pearson相关分析示，初发RA患者PBMC中miR-21表达与CCP、DAS28评分呈负相关关系(p均 < 0.05)。初发RA患者PBMC中miR-21表达与STAT3mRNA表达呈负相关关系(p均 < 0.05)。ROC曲线分析显示，PBMC中miR-21、CCP表达诊断RA的曲线下面积(AUC)分别为0.7531、0.8338，二者联合诊断的AUC为0.8950。结论：RA患者PBMC miR-21表达降低，STAT3mRNA表达升高，两者可能参与RA发生、发展。RA患者CCP联合miR-21对RA发生有一定的临床诊断价值。

Abstract: Objective: To investigate the changes of miR-21 and STAT3mRNA expression inperipheral blood mononuclear cells (PBMC) of patients with newly diagnosed rheumatoid arthritis (RA) before and after treatment with tofacitinib and their clinical significance. Methods: Sixty patients with newly diagnosed RA and 40 healthy controls (HC) were enrolled in this study. Patients with newly diag-nosed RA were treated with methotrexate (MTX) for 3 months. After 3 months, the patients who were poorly controlled with MTX alone were treated with tofacitinib and followed up for 3 months. The expressions of miR-21 and STAT3mRNA in PBMC were detected by qRT-PCR. The laboratory examination data of the two groups were observed and recorded, including erythrocyte sedimen-tation rate (ESR), high-sensitivity C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (CCP), and disease activity score 28 (DAS28). Results: The expression of miR-21 in PBMC of RA patients was significantly lower than that of healthy people, while STAT3mRNA expression was significantly higher than that of healthy people (all p < 0.01). Compared with MTX alone, the expression of miR-21 in PBMC increased, while the expression of STAT3mRNA decreased in tofacitinib plus MTX group (all p < 0.01). Pearson correlation analysis showed that the expression of miR-21 in PBMC of RA patients was negatively correlated with CCP and DAS28 scores (all p < 0.05). There was a negative correlation between the expression of miR-21 and STAT3mRNA in PBMC of newly diagnosed RA patients (p < 0.05). ROC curve analysis showed that the area under the curve (AUC) of miR-21 and CCP expression in PBMC for the diagnosis of RA was 0.7531 and 0.8338, respectively, and the AUC of combined diagnosis of miR-21 and CCP was 0.8950. Conclusion: The expression of miR-21 in PBMC of RA patients is decreased, and the ex-pression of STAT3mRNA is increased, which may be involved in the occurrence and development of RA. CCP combined with miR-21 has a certain clinical diagnostic value for the occurrence of RA.