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Received:April 06, 2021 Published Online:October 20, 2021
Received:April 06, 2021 Published Online:October 20, 2021
中文摘要: 目的 研究二甲双胍对类风湿关节炎（RA）患者外周血CD4+T淋巴细胞亚群的影响，探讨其临床意义。
方法 采用开放型前瞻性研究方法，收集2018年10月至2020年8月在山西省汾阳医院风湿免疫科就诊的54例疾病活动期RA患者，使用随机数余数分组法分为两组，试验组28例，给予二甲双胍联合或不联合改善病情抗风湿药（DMARDs）治疗；对照组26例，予传统DMARDs治疗。采用流式细胞术分别检测治疗0、3、6月时外周血CD4+T淋巴细胞亚群，比较治疗前后试验组CD4+T细胞亚群水平的变化，记录DMARDs使用情况和药物不良反应，评估二甲双胍在RA中的安全性和有效性。
结果组内比较，二甲双胍治疗3个月、6个月，试验组外周血调节性T细胞（Treg）较治疗前显著升高（ Z =2.733、2.573， P =0.006、0.010）；辅助T细胞17（Th17）/Treg较治疗前显著下降（ Z =2.619、2.164， P =0.009、0.030）；二甲双胍治疗6个月，试验组Th1较治疗前显著升高（ Z =3.917， P <0.01）。治疗6个月，试验组外周血Th1、Th2、Treg显著高于对照组（ Z =3.090、2.242、3.705， P =0.002、0.025、 P <0.01），Th17/Treg稍低于对照组但差异无统计学意义（ Z =1.724， P =0.085）。试验组治疗6个月与治疗前比较，28个关节肿胀数（SJC）和28个关节压痛数（TJC）较治疗前明显减少（ Z =3.606、3.998， P <0.01），28个关节疾病活动评分（DAS28）较治疗前明显下降（ Z =3.507， P <0.01）；疼痛视觉模拟评分（VAS）和疾病活动指数（CDAI）均明显下降（ Z =3.622、3.972， P <0.01）。未出现不可逆的或严重不良反应。
结论 二甲双胍可促进RA患者外周血CD4+T淋巴细胞中Treg细胞增长，使Th17/Treg下降并维持平衡，有利于病情缓解且安全性良好。
Abstract:Objective To investigate the effect and its clinical significance of metformin on CD4+ T lymphocyte subsets in peripheral blood of patients with rheumatoid arthritis (RA).
Methods Using open prospective research method, 54 patients with active RA treated from October 2018 to August 2020 were selected and randomly divided into two groups. The patients treated with metformin combined with or without conventional disease-modifying anti-rheumatic drugs (DMARDs) were selected as experimental group( n =28),and the patients treated with conventional DMARDs were served as control group ( n =26). CD4+T lymphocyte subsets in peripheral blood were detected by flow cytometry at 0-,3-and 6-month, respectively and were compared with those before treatment. The use of DMARDs and adverse drug reactions were observed to evaluate the safety and efficacy of metformin in treating RA.
Results After 3-and 6-months of treatment in experimental group, the levels of peripheral blood regulatory T cells (Treg) were significantly higher than those before treatment ( Z =2.733, P =0.006； Z =2.573, P =0.010),and T helper 17 cells (Th17) / Treg levels were significantly lower than those before treatment ( Z =2.619, P =0.009； Z =2.164， P =0.030). After 6 months of treatment, Th1 level in experimental group was significantly higher than that before treatment ( Z =3.917, P <0.01). The levels of Th1（ Z =3.090, P =0.002）,Th2( Z =2.242, P =0.025) and Treg（ Z =3.705, P <0.01）were significantly higher in experimental group than those in control group after 6 months of treatment. Th17/Treg was slightly lower than that in control group, but there was no statistical difference in it between two groups ( Z =1.724, P =0.085). Compared with those before treatment, the number of swollen joint count (SJC, Z =3.606) and tender joint count (TJC, Z =3.998), the 28-joint disease activity score (DAS28, Z =3.507), pain visual analogue scale (VAS, Z =3.622) and clinical disease activity index （CDAI, Z =3.972）significantly decreased after 6 months of treatment in experimental group ( P <0.01）. There were no irreversible or serious adverse reactions in two groups.
Conclusion Metformin could promote the proliferation of CD4+Treg cells in peripheral blood and maintain Th17/Treg balance, which is conducive to disease remission with good safety in RA patients.
keywords: Rheumatoid Arthritis Metformin CD4+T lymphocyte subsets Regulatory T cells T helper 17 cells
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基金项目:山西省吕梁市科技重点研发项目（2018shfz65-7）；山西医科大学汾阳学院科技发展重点项目（2019C07）
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