南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (02): 127-.doi: 10.12122/j.issn.1673-4254.2019.02.01

• •    下一篇

二甲双胍治疗白塞病的临床疗效、安全性和调节Treg/Th17平衡的作用：30例前瞻性研究

陈永，罗丹，林晨红，申艳，蔡剑飞，管剑龙   

  • 出版日期:2019-02-20 发布日期:2019-02-20

Efficacy and safety of metformin for Behcet’s disease and its effect on Treg/Th17 balance: a single-blinded, before-after study

  • Online:2019-02-20 Published:2019-02-20

HTML

PDF

1899

摘要： 目的观察二甲双胍治疗白塞病（Behcet病，BD）的临床疗效、安全性以及调节Treg/Th17平衡的作用。方法本研究对30 例BD病患者进行前瞻性单盲和历史对照研究，记录二甲双胍治疗前后患者粘膜皮肤活动指数（MAIBD）、复发频率、C-反应蛋 白（CRP）和红细胞沉降率（ESR）的变化；同时测定Foxp3、白介素-35（IL-35）、转化生长因子-β（TGF-β）、Ror-γt、IL-17和肿瘤坏死 因子-α（TNF-α）的蛋白和mRNA的表达水平变化。结果共有26 例患者完成了研究，其中88.46%（23/26）的患者治疗效果满 意，11.54%（4/26）的患者获得部分缓解。治疗中26.67%（8/30）的患者出现胃肠道副作用，并且由于副作用，第一周有4名患者 退出研究。我们的研究结果表明二甲双胍治疗后患者的MAIBD和复发频率降低；此外，CRP和ESR的临床炎症指标均有所下 降，差异有统计学意义。ELISA和qRT-PCR结果显示，治疗后患者Foxp3 和TGF-β蛋白和相对mRNA表达水平增加，而作为 Th17标志物的ROR-γt，IL-17和TNF-α水平降低；另外，二甲双胍治疗后患者IL-35水平也有所降低。结论二甲双胍有助于缓 解BD患者的症状，可降低炎症反应指标，调节Treg/Th17轴，可作为治疗BD的潜在候选药物。 中国临床试验注册：ChiCTR-ONC-16009621。注册时间：2016-10-26

Abstract: Objective Behcet’s disease (BD) is an autoimmune disorder that causes most commonly mouth and genital ulcerations and erythema nodules of the skin and currently has limited options of therapeutic medicines. Metformin is recently reported to suppress immune reaction, and we hypothesized that metformin could be an option for treatment of BD. Methods Thirty patients with BD were enrolled in this perspective single-blinded, before-after study. We recorded the changes in the mucocutaneous activity index for BD (MAIBD), relapse frequency, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) after metformin treatment to assess the changes in the disease activity. We also analyzed the changes in the protein and mRNA expression levels of Foxp3, interleukin-35 (IL-35), transforming growth factor-β (TGF-β), Ror-γt, IL-17, and tumor necrosis factor-α (TNF-α) in these patients using ELISA and qRT-PCR. Results Of the 30 patients enrolled, 26 completed the trial. After the treatment, favorable responses were achieved in 88.46% (23/26) of the patients, and partial remission was obtained in 11.54% (4/26) of them. During the treatment, 8 patients complained of gastrointestinal side effects, for which 4 chose to withdraw from the study in the first week. Our results showed that metformin treatment decreased MAIBD and relapse frequency in the patients, and significantly lowered the clinical inflammatory indexes including CRP and ESR. The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-β expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-γt, IL-17 and TNF-α as well as IL-35 level in these patients. Conclusion Metformin treatment relieves the clinical symptoms, reduces the inflammatory reaction indexes and regulates the Treg/Th17 axis in patients with BD, suggesting the potential of metformin as a candidate medicine for treatment of BD. Chinese Clinical Trial Registry: ChiCTR-ONC-16009621. Date of Registration: 2016-10-26.