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温化蠲痹方对类风湿关节炎患者外周血单个核细胞微小RNA-146a、DNA甲基化转移酶表达的影响 被引量:15

Effects of Wenhua Juanbi Recipe on the Expressions of miRNA-146a and DNA Methyltransferases in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis
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摘要 目的观察温化蠲痹方对活动期类风湿关节炎(rheumatoid arthritis,RA)患者外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)微小RNA-146a (miRNA-146a)、DNA甲基化转移酶(DNA methyltransferases,DNMTs)表达影响及miRNA-146a与DNMTs表达的相关性。方法采用随机数字表法,将60例RA患者随机分为两组:中药温化蠲痹方加西药治疗组(简称治疗组,30例)及对照组(30例)。其中对照组口服甲氨蝶呤片(MTX,每周1次,每次7.5 mg),来氟米特片(LEF,每天1次,每次10 mg),美洛昔康片(每天1次,每次7.5 mg)。治疗组在对照组治疗的基础上,加用温化蠲痹方,每天1剂,分2次口服,疗程12周。观察两组临床疗效、治疗前后症状、体征,包括中医证候疗效分析、健康状况评估(HAQ评分)、疾病活动指数(DAS28)、患者疼痛评估(VAS评分)、晨僵时间等,检测血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗CCP抗体)、血小板(PLT)计数,运用实时定量PCR方法检测外周血miRNA-146a与DNMTs表达。结果治疗组总有效率[90.0%(27/30)]优于对照组[80.0%(24/30),P<0.05]。与对照组比较,治疗组ACR20、ACR50达标率(分别为43.3%、36.7%)高于对照组(33.3%、26.7%,P<0.05);治疗组DAS28、HAQ评分、VAS评分降低,关节肿胀数、关节压痛数减少、晨僵时间缩短(P<0.05,P<0.01);miRNA-146a、DNMTs、ESR、CRP、RF、抗CCP抗体、PLT计数差异均有统计学意义(P<0.05,P<0.01);活动期RA患者PBMCs DNMTs表达水平降低(P<0.01)、miRNA-146a表达水平升高(P<0.01),miRNA-146a表达水平与DNMT1(r=-0.362,P=0.04)、DNMT3a(r=-0.566,P=0.01)、DNMT3b(r=-0.382,P=0.03)呈负相关。治疗组出现肝酶升高、胃肠道反应等不良反应明显降低(P<0.05)。结论 中药温化蠲痹方加西药治疗RA疗效优于单纯西药治疗组,其机制可能与下调活动期RA患者miRNA-146a表达、上调DNMTs表达有关。 Objective To observe the effects of Wenhua Juanbi Recipe (WJR) on the expressions of miRNA-146a and DNA methyltransferases (DNMTs) in peripheral blood mononuclear cells (PB- MCs) of patients with active rheumatoid arthritis (RA), and the correlation between miRNA-146a and DNMTs. Methods Sixty RA patients were assigned to the treated group and the control group by random number table, 30 in each group. Patients in the control group took methotrexate (MTX, 7.5 mg each time, once per week), leflunomide (LEF, 10 mg each time, once per day), and meloxicam (Mobic, 7.5 mg each time, once per day). Those in the treated group took W JR additionally, one dose per day, taken in two portions. The therapeutic course for both groups was 12 weeks. Clinical effect, symptoms and physical signs [ (including efficacy analyses of TCM symptoms and syndrome, Health Assessment Questionnaire (HAQ score), disease activity score (DAS 28), visual analogue scale (VAS), morning stiffness time], and laboratory indices [ erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor ( RF), anti-CCP antibody, platelet count (PLT) ] were observed in two groups after treatment. The expression levels of microRNA-146a and DNMTs in PBMCs were detected by real- time quantitative PCR assay. Results The total effective rate was higher in the treated group than in the control group [90.0% (27/30) vs 80.0% (24/30), P 〈0.05]. The standard rates of ACR20 and ACR50 were higher in the treated group than in the control group (43.3% vs 33.3%, 36.7% vs 26.7%, P 〈 0.05). DAS28, HAQ score, and VAS decreased, swollen joints number and tender joints number were reduced, morning stiffness time was shortened in the treated group (P 〈0.05, P 〈0.01 ). There was statistical difference in miRNA-146a, DNMTs, ESR, CRP, RF, anti-CCP antibody, or PLT between the two groups (P 〈0.05, P 〈0.01 ). The expression of DNMTs decreased and the expression of miRNA-146a increase
作者 刘喜德 刘敏 蔡龙 周红娟 王珊珊 叶丽红 杜静 王安琪 贺利群 郑琳琳 LIU Xi-de;LIU Min;CAI Long;ZHOU Hong-juan;WANG Shan-shan;YE Li-hong;DU Jing;WANG An-qi;HE Li-qun;ZHENG Lin-lin(Department of Athropathy,Zhejiang Provincial Hospital of Integrated Traditional and Western Medicine,Hangzhou(310003;Second Clinical Medical College,Zhejiang Chinese Medical University,Hangzhou(310053)
出处 《中国中西医结合杂志》 CAS CSCD 北大核心 2018年第11期1320-1326,共7页 Chinese Journal of Integrated Traditional and Western Medicine
基金 浙江省自然科学基金资助项目(No.LY17H270004 No.LY12H29008) 浙江省中医药科技计划项目(No.2012ZB121 No.2015ZA143) 杭州市医药卫生科技计划项目(No.2014A37) 杭州市科技发展计划(No.20160533B45)
关键词 温化蠲痹方 类风湿关节炎 miRNA-146a DNA甲基化转移酶 Wenhua Juanbi Recipe rheumatoid arthritis miRNA-146a DNA methyltransferases
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