Th17/Treg平衡与正常妊娠及子痫前期关系的研究

The role of Th17/Treg balance in normal pregnancy and preeclampsia

目的:探讨Th17及CD4+CD25+Foxp3+调节性T(regulatory T,Treg)细胞介导的免疫反应在子痫前期发病中的作用。方法:选取在山东大学齐鲁医院进行产前检查的子痫前期患者25例及正常晚孕期妇女27例,并选取育龄期健康未孕妇女20例。利用流式细胞技术检测3组患者血样中分泌IL-17的Th17及CD4+CD25+Foxp3+Treg细胞亚群占CD4+T淋巴细胞的百分比,并计算Th17/Treg比率,比较其在子痫前期与正常妊娠时的变化;再用酶联免疫吸附试验(ELISA)检测3组患者外周血中IL-17、IL-10、TGF-β1等细胞因子的表达并进行比较。结果:(1)与正常未孕组及正常妊娠组相比,子痫前期患者外周血中分泌IL-17的Th17细胞占CD4+T淋巴细胞百分比明显升高(P<0.01),CD4+CD25+Foxp3+Treg细胞占CD4+T淋巴细胞百分比明显降低(P<0.01);与正常未孕组相比,正常妊娠组Th17细胞的比例明显降低(P<0.01),Treg细胞比例明显升高(P<0.05);(2)子痫前期患者外周血中Th17/Treg比率明显高于正常未孕组及正常妊娠组(P<0.01),正常妊娠组外周血中Th17/Treg比率与健康未孕组相比明显降低(P<0.01);(3)子痫前期患者外周血中IL-17及TGF-β1的TGF-β1表达明显高于正常未孕组及正常妊娠组(P<0.05),而IL-10的表达未见明显差异(P>0.05);与正常未孕组相比,正常妊娠组外周血中IL-17、IL-10及TGF-β1的水平均未见明显变化(P>0.05)。结论:正常妊娠可能依赖于Treg细胞介导的免疫耐受状态,子痫前期患者外周血中Th17/Treg之间的平衡失调而倾向于Th17介导的促炎状态,这一机制可能参与了子痫前期的发生发展。

Objective：To investigate the role of immune response induced by T-helper 17 and CD4＋CD25＋Foxp3＋regulatory T（Treg）cell in the pathogenesis of preeclmpsia.Methods：A total of 25 preeclampsia patients and 27 healthy late-pregnant women who underwent antenatal examinations in Qilu hospital,Shandong University and 20 healthy non-pregnant women were inrolled in this study.We examined and compared the frequencies of IL-17-producing CD4＋cells as Th17 and CD4＋CD25＋Foxp3＋Treg cells which were expressed as a percentage of the total CD4＋cells and also the Th17/Treg ratio in peripheral blood samples in both preeclampsia patients and healthy late-prengnant women by Flow cytometric,and the expressions of of IL-17,IL-10,and TGF-β1 in serum by Enzyme linked immunosorbent assay（ELISA）.Results：（1）Compared to both non-pregnant and normal pregnant group,the percentage of IL-17-producing CD4＋T cells as Th17 in the total CD4＋T cells in peripheral blood samples of the pre-eclampsia group was significantly increased（P0.01）,while the percentage of CD4＋CD25＋Foxp3＋Treg cell in the total CD4＋T cells was strikingly decreased（P0.01）;when compared to the non-pregnant group,the frequency of Th17 cell in normal pregnant group was significantly decreased than in non-pregnant women（P0.01）,while the proportion of Treg cells was notably elevated（P0.05）;（2）Compared to both non-pregnant and normal pregnant group,the Th17/Treg ratio in pre-eclampsia patients was impressively increased（P0.01）,and the ratio in healthy late-pregnant women was notably lower than in non-pregnant women（P0.01）.（3）Compared to both non-pregnant and normal pregnant group,the expressions of IL-17 and TGF-β1 were evidently higher in pre-eclampsia group（P0.05）,while the expression of IL-10 in blood simples of the normal pregnant group was imperceptibly increased（P0.05）;and there were slight detectable changes in the concentrations of IL-17 and TGF-β1 in normal pregnant group when compared with the non-pregnant group.Conclusion：There is a shift in the Th17/Treg balance favouring skewness towards a pro-inflammatory status in preeclampsia,the imbalance of Th17/Treg may be involved in the development and progression of preeclampsia.