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中国尿毒症血液透析患者 Treg/Th17 功能失衡:钙化与心血管疾病的关联。

Treg/Th17 functional disequilibrium in Chinese uremia on hemodialysis: a link between calcification and cardiovascular disease.

机构信息

Department of Nephrology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.

出版信息

Ren Fail. 2012;34(6):697-702. doi: 10.3109/0886022X.2012.672155. Epub 2012 Apr 13.

Abstract

AIM

To investigate the correlation of the functional disequilibrium of regulatory T cells (Treg)/T-helper (Th17) cells with calcification and to explore the significance of their influence on the outcome of cardiovascular disease (CVD) in uremic patients after hemodialysis (HD).

METHODS

Out of 66 uremia patients, 36 patients had CVD after HD (maintenance hemodialysis (MHD) group1) and 30 patients did not have CVD (MHD group2). Twenty healthy volunteers were selected as normal control group. Peripheral blood mononuclear cells were isolated and treated with recombinant human bone morphogenetic protein-2 (rhBMP-2). Treg and Th17 frequencies were measured by flow cytometry. Forkhead/winged helix transcription factor (Foxp3) and retinoic acid receptor-related orphan receptor-γt (ROR-γt) mRNA expressions were measured by real-time quantitative polymerase chain reaction. Levels of interleukin (IL)-10 and IL-17 were detected by enzyme-linked immunosorbent assay.

RESULTS

When compared with controls, rhBMP-2 upregulates Treg/Th17 functional disequilibrium in uremia patients, displaying higher Treg and Th17 frequencies, Foxp3 and ROR-γt expressions, and levels of cytokines (p < 0.05). These differences were also significant between MHD group1 and group2 (p < 0.05). It was also observed that Treg/Th17 functional disequilibrium was not only correlated with a calcification state but also consistent with the CVD.

CONCLUSION

The Treg/Th17 cell function disequilibrium might act synergistically with calcification in the high incidence of CVD after HD.

摘要

目的

探讨调节性 T 细胞(Treg)/辅助性 T 细胞 17(Th17)功能失衡与钙化的相关性,并探讨其对血液透析(HD)后尿毒症患者心血管疾病(CVD)结局的影响意义。

方法

选择 66 例尿毒症患者,其中 36 例 HD 后发生 CVD(维持性血液透析(MHD)组 1),30 例未发生 CVD(MHD 组 2)。选择 20 例健康志愿者作为正常对照组。分离外周血单个核细胞,用重组人骨形态发生蛋白-2(rhBMP-2)处理。采用流式细胞术检测 Treg 和 Th17 频率。实时定量聚合酶链反应检测叉头/翼状螺旋转录因子(Foxp3)和维甲酸受体相关孤儿受体-γt(ROR-γt)mRNA 表达。酶联免疫吸附试验检测白细胞介素(IL)-10 和 IL-17 水平。

结果

与对照组相比,rhBMP-2 上调尿毒症患者 Treg/Th17 功能失衡,表现为 Treg 和 Th17 频率较高、Foxp3 和 ROR-γt 表达水平较高、细胞因子水平较高(p<0.05)。MHD 组 1 与组 2 之间也存在显著差异(p<0.05)。还观察到 Treg/Th17 功能失衡不仅与钙化状态相关,而且与 CVD 一致。

结论

Treg/Th17 细胞功能失衡可能与 HD 后 CVD 高发时的钙化协同作用。

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