【摘要】 目的:观察艾拉莫德联合甲氨蝶呤治疗难治性类风湿关节炎(RA)的疗效及对患者血清微小RNA-141(miR-141)和miR-335-5p表达的影响。方法:将难治性RA患者80例随机分为甲氨蝶呤组(单纯甲氨蝶呤治疗，40例)和联合艾拉莫德组(艾拉莫德联合甲氨蝶呤治疗，40例),均治疗3个月。比较两组临床疗效、免疫功能指标、骨代谢指标、炎症因子水平、症状改善情况以及miR-141和miR-335-5p表达水平。记录治疗期间不良反应发生情况。结果:联合艾拉莫德组总有效率高于甲氨蝶呤组(P<0.05)。两组血清免疫球蛋白G(IgG)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、Ⅰ型胶原交联羧基末端肽(CTX-Ⅰ)、类风湿因子(RF)、分泌型糖蛋白-3α(Wnt-3α)、白细胞介素-1(IL-1)、IL-6、C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、miR-141水平，以及28个关节疾病活动度(DAS28)评分、关节压痛指数、关节肿胀指数较治疗前降低，且联合艾拉莫德组低于甲氨蝶呤组(均P<0.05)。血清miR-335-5p、骨碱性磷酸酶(B-ALP)水平较治疗前升高，且联合艾拉莫德组高于甲氨蝶呤组(均P<0.05)。晨僵时间较治疗前缩短，且联合艾拉莫德组短于甲氨蝶呤组(均P<0.05)。治疗期间，联合艾拉莫德组与甲氨蝶呤组总不良反应发生率比较差异无统计学意义(P>0.05)。结论:相较于单纯甲氨蝶呤治疗，艾拉莫德联合甲氨蝶呤可进一步改善难治性RA患者免疫功能，改善相关细胞因子水平及炎症反应，缓解患者症状，同时具有良好安全性。艾拉莫德的治疗作用可能与调控血清miR-141、miR-335-5p水平有关。更多还原

【Abstract】 Objective:To observe the efficacy of iguratimod combined with methotrexate in the treatment of refractory rheumatoid arthritis(RA) and its effect on the expressions of microRNA-141(miR-141) and miR-335-5p.Methods:A total of 80 patients with refractory RA were randomly divided into methotrexate group(treated with MTX alone, 40 cases) and combined iguratimod group(treated with iguratimod combined with MTX,40 cases).All patients were treated for 3 months.The clinical efficacy, immune function indexes, bone metabolism indexes, inflammatory factor levels, symptom improvement, and expression levels of miR-141 and miR-335-5p were compared between the two groups.The occurrence of adverse reactions during the treatment was recorded.Results:The combined iguratimod group had a significantly higher overall response rate than the methotrexate group(P<0.05).The serum levels of IgG,IgA,IgM,CTX-Ⅰ,RF,Wnt-3α,IL-1,IL-6,CRP,TNF-α,miR-141,and DAS28 score, joint tenderness index and joint swelling index in two groups were lower than those before treatment, and those in combined iguratimod group were lower than those in methotrexate group(all P<0.05).The levels of serum miR-335-5p and B-ALP were higher than those before treatment, and those in combined iguratimod group were higher than those in methotrexate group(all P<0.05).The duration of morning stiffness in combined iguratimod group was shorter than that in methotrexate group(all P<0.05).During the treatment, there was no significant difference in total incidence of adverse reactions between two groups(P>0.05).Conclusion:Compared with methotrexate alone, iguratimod combined with methotrexate can further improve the immune function of patients with refractory RA,improve the levels of related cytokines and inflammatory response, relieve the symptoms of patients, and has a good safety profile.The therapeutic effect of iguratimod may be related to the regulation of serum miR-141 and miR-335-5p levels.更多还原