上海交通大学学报(医学版)

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脂联素对不明原因复发性流产患者外周血Th17/Treg细胞分群及细胞因子水平的影响

李维宏,牟晓玲   

  1. 重庆医科大学附属第一医院妇产科, 重庆 400016
  • 出版日期:2015-07-28 发布日期:2015-08-27
  • 作者简介:李维宏(1977—), 女, 主治医师, 博士; 电子信箱: liweihong_1211@yahoo.com。
  • 基金资助:

    重庆市卫生局医学科研项目(2012-2-029)

Effects of adiponectin on populations of peripheral blood Th17/Treg cells and cytokine levels of patients with unexplained recurrent spontaneous abortion

LI Wei-hong, MOU Xiao-ling   

  1. Department of Gynaecology and Obstetrics, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China
  • Online:2015-07-28 Published:2015-08-27
  • Supported by:

    Medical Scientific Research Project of Chongqing Municipal Health Bureau, 2012-2-029

摘要:

目的  探讨脂联素对不明原因复发性流产(URSA)患者外周血Th17/调节性T细胞(Treg)平衡的调节作用。方法  以URSA患者为研究对象,健康未孕和正常妊娠女性为对照,分离血清及外周血单个核细胞(PBMC),ELISA法检测血清脂联素及Th17/Treg相关细胞因子白介素17(IL-17)和转化生长因子β(TGF-β)水平,流式细胞术观察Th17/Treg细胞分群。以不同浓度的脂联素对URSA患者PBMC进行体外干预,ELISA法检测PBMC培养上清液中IL-17和TGF-β水平,流式细胞术观察Th17/Treg分群的变化,real-time PCR检测转录因子RORγtFOXP3 mRNA表达水平。结果  URSA患者血清脂联素水平显著降低且Th17/Treg失衡。经脂联素体外处理,URSA患者PBMC中Treg细胞比例增加,Th17细胞比例减少;培养上清液中TGF-β水平升高,IL-17水平降低;细胞FOXP3 mRNA表达上调,RORγt mRNA表达下调。上述效应均呈一定的剂量依赖性。结论  URSA患者体内存在脂联素缺乏和Th17/Treg失衡。脂联素体外处理可呈剂量依赖性地改善URSA患者PBMC中Th17/Treg失衡,提示脂联素可能通过调节Th17/Treg平衡保护妊娠。

关键词: 脂联素, 不明原因复发性流产, Th17, 调节性T细胞

Abstract:

Objective  To investigate the regulating effect of adiponectin on the balance of Th17/regulatory T cells (Treg) in peripheral blood of patients with unexplained recurrent spontaneous abortion (URSA). Methods  URSA patients were selected as subjects and healthy nonpregnancy and normal pregnancy women were selected as controls. Serum and peripheral blood mononuclear cells (PBMCs) were isolated. The levels of serum adiponectin, interleukin 17 (IL-17), and transforming growth factor-β (TGF-β) were detected by ELISA. The populations of Th17/Treg cells were observed by flow cytometry. PBMCs of URSA patients were treated by adiponectin of different concentrations in vitro and the levels of IL-17 and TGF-β in supernatant were detected by ELISA, the change of populations of Th17/Treg cells was observed by flow cytometry, and the mRNA expressions of transcription factors RORγt and FOXP3 were detected by real-time PCR. Results  Serum adiponectin levels of URSA patients significantly decreased and the imbalance of Th17/Treg was found. Adiponectin treatment increased the ratio of Treg cells, decreased the ratio of Th17, increased TGF-β level in culture supernatant, decreased IL-17 level, up-regulated mRNA expression of FOXP3, and down-regulated mRNA expression of RORγt. These effects were all dose-dependent. Conclusion  Deficiency of adiponectin and imbalance of Th17/Treg exist in patients with URSA. Adiponectin treatment in vitro can dose-dependently ameliorate the imbalance of Th17/Treg in PBMC of patients with URSA, suggesting that adiponectin may protect the pregnancy by regulating the balance of Th17/Treg.

Key words: adiponectin, unexplained recurrent spontaneous abortion, Th17, regulatory T cells