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桥本甲状腺炎患者外周血调节性T细胞/Th17细胞平衡动态变化的研究

The dynamic changes of Treg/Th17 cells imbalance in patients with Hashimoto thyroiditis

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【作者】 薛海波马蕾王秀云刘俊英刘长梅张立

【Author】 XUE Hai-bo,MA Lei,WANG Xiu-yun,LIU Jun-ying,LIU Chang-mei,ZHANG Li.Department of Endocrinology and Metabolism,Affiliated Hospital of Binzhou Medical College,Binzhou 256603,China

【机构】 滨州医学院附属医院内分泌与代谢病科滨州医学院附属医院皮肤科

【摘要】 目的探讨桥本甲状腺炎(HT)患者外周血调节性T细胞(Treg)与Th17细胞的动态变化及其意义。方法流式细胞术检测36例HT患者[HT组,根据甲状腺功能分为A(18例)、B(10例)、C(8例)3个亚组]和30例健康对照者外周血单个核细胞(PBMC)中Treg和Th17细胞的比例,实时定量RT-PCR检测Treg和Th17细胞特异性转录因子Foxp3、RORγt mRNA的表达水平,ELISA检测血清中相关细胞因子TGF-β和IL-17A的含量。结果 HT患者PBMC中Treg细胞比例及Foxp3 mRNA表达水平均明显低于健康对照者(t=-10.62、-7.624,P均<0.01),HT亚组间差异具有统计学意义(F=4.414、4.512,P均<0.05);Th17细胞比例、RORγtmRNA表达水平及Th17/Treg比值均明显高于健康对照者(t=11.32、19.25、8.386,P均<0.01),HT亚组间差异均具有统计学意义(F分别为34.947、14.551、24.338,P均<0.01),亚组间两两比较差异均有统计学意义(P均<0.05)。HT患者血清TGF-β的含量较健康对照者略低,但差异无统计学意义(P>0.05);IL-17A的含量均较健康对照者显著升高(P<0.01),HT患者组内各亚组间血清IL-17A的含量差异具有统计学意义(F=11.077,P<0.01),两两比较差异亦具有统计学意义(P均<0.05)。HT患者Th17/Treg比值与血清甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)滴度均呈显著正相关(r=0.349、0.502,P=0.037、0.002)。结论在HT发病过程中,Th17/Treg细胞轴呈动态改变,并且与甲状腺自身抗体滴度正相关,说明Th17/Treg细胞亚群的免疫失平衡可能参与了HT的发生发展。

【Abstract】 Objective To investigate the dynamic changes and significance of regulatory T cells(Treg)and Th17 cells in patients with Hashimoto thyroiditis(HT).Methods 36 HT patients[18 cases with euthyroidism(subset A),10 cases with subclinical hypothyroidism(subset B),8 cases with overt hypothyroidism(subset C)]and 30 healthy controls(NC)were selected.Flow cytometry was performed to detect the percentages of Treg and Th17 cells.Real-time RT-PCR was employed to analyze the expressions of Foxp3 and RORγt mRNA.Serum concentrations of TGF-β and IL-17A were measured by ELISA.Results Treg cells percentages and Foxp3 mRNA levels decreased obviously in HT patients(t=-10.62,-7.624 respectively and both P<0.01),one-way ANOVA test in A,B and C subsets revealed that the differences were significant(F=4.414,4.512 respectively and both P<0.05),and a significant increase in Th17 cells percentages,RORγt mRNA levels and the ratio of Th17/Treg cells(t=11.32,19.25,8.386 respectively and all P<0.01)compared with NC,one-way ANOVA test in A,B and C subsets revealed that the differences were significant(F=34.947,14.551,24.338 respectively and all P<0.01),and multiple comparison in A,B and C subsets revealed that the differences were significant(all P<0.05).There was no statistical difference in serum concentration of TGF-β between HT and NC(P>0.05),while IL-17A levels increased markedly in HT patients(P<0.01).In HT patients,the ratio of Th17/Treg cells positively correlated with the levels of serum thyroperoixidase antibody(TPOAb),thyroglobulin antibody(TgAb)(r=0.349,0.502 and P=0.037,0.002 respectively).Conclusions During the process of HT,there were dynamic changes of Th17/Treg cells,and positively correlated with the thyroid specific autoantibodies,which may lead to immune imbalance and contribute to the development of HT.

【基金】 山东省科技发展计划(2011YD18063);山东省自然科学基金(ZR2010HQ013);山东省高等学校科技计划项目(J10LF90,J11LF66);滨州医学院科研启动基金(BY2009KYQD03,BY2010KYQD04)
  • 【文献出处】 中华临床医师杂志(电子版) ,Chinese Journal of Clinicians(Electronic Edition) , 编辑部邮箱 ,2012年08期
  • 【分类号】R581
  • 【被引频次】36
  • 【下载频次】307
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