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重组人骨形态发生蛋白-2及调节性T细胞/辅助性T细胞17功能失衡在维持性血液透析后并发心血管疾病的尿毒症患者中的作用

The effects of rhBMP-2 and Treg/Th17 functional disequilibrium in uremic patients with cardiovascular complication after maintenance hemodialysis.

作者信息

Danyan Chen, Xiaolong Huang, Song Lu, Hua Gan, Weixue Tang, Ke Liu

机构信息

Department of Endocrinology & Nephrology, the Chongqing Zhongshan Hospital, Chongqing, China.

出版信息

Int J Artif Organs. 2013 Jul;36(7):464-72. doi: 10.5301/ijao.5000217. Epub 2013 May 16.

Abstract

OBJECTIVES

We compared the correlation of regulatory T cell (Treg) and Th17 cell function disequilibrium with calcification in uremic patients on maintenance hemodialysis (MHD) with healthy controls, and investigated if their influence possibly increased the development and outcome of cardiovascular complications in uremic patients after MHD.

METHODS

The extent of coronary artery calcification was assessed by coronary artery calcification scoring (CACS) in uremic patients with and without adverse cardiovascular events after MHD (MHD group 1 vs. MHD group 2, respectively). Peripheral blood mononuclear cells were incubated with rhBMP-2 as positive control. The Treg/Th17 cell frequencies, Foxp3 ROR-gt mRNA expressions, and MIP 3α/CCL20 concentrations were measured.

RESULTS

The CACS score was significantly higher in MHD group 1 as compared group 2. In comparison with controls, rhBMP-2 upregulates Treg/Th17 functional disequilibrium in uremic patients, displayed higher Treg and Th17 frequencies, Foxp3 and ROR-gt expressions, and MIP3α/CCL20 concentrations. However, the up-regulations of Treg frequencies and Foxp3 expressions were significant in controls but not in MHD patients. It was also observed that Treg/Th17 functional disequilibrium was not only correlated with rhBMP-2 state but also consistent with the cardiovascular complications. Moreover, the CACS was negatively correlated with Treg cell frequencies but positively correlated with Th17 cell frequencies and MIP3a/CCL20 concentrations.

CONCLUSIONS

Function disequilibrium of Treg/Th17 was related to the degree of the rhBMP-2 state. Function disequilibrium of the Treg/Th17 might act synergistically with rhBMP-2 in the high incidence of immune-mediated cardiovascular complications after MHD.

摘要

目的

我们比较了维持性血液透析(MHD)的尿毒症患者与健康对照者中调节性T细胞(Treg)和Th17细胞功能失衡与钙化的相关性,并研究其影响是否可能增加MHD后尿毒症患者心血管并发症的发生和预后。

方法

通过冠状动脉钙化评分(CACS)评估MHD后有和无不良心血管事件的尿毒症患者的冠状动脉钙化程度(分别为MHD组1和MHD组2)。将外周血单个核细胞与重组人骨形态发生蛋白-2(rhBMP-2)一起孵育作为阳性对照。检测Treg/Th17细胞频率、Foxp3和ROR-γt mRNA表达以及MIP 3α/CCL20浓度。

结果

与MHD组2相比,MHD组1的CACS评分显著更高。与对照组相比,rhBMP-2上调了尿毒症患者的Treg/Th17功能失衡,表现为Treg和Th17频率、Foxp3和ROR-γt表达以及MIP3α/CCL20浓度更高。然而,Treg频率和Foxp3表达的上调在对照组中显著,但在MHD患者中不显著。还观察到Treg/Th17功能失衡不仅与rhBMP-2状态相关,而且与心血管并发症一致。此外,CACS与Treg细胞频率呈负相关,但与Th17细胞频率和MIP3α/CCL20浓度呈正相关。

结论

Treg/Th17的功能失衡与rhBMP-2状态的程度有关。Treg/Th17的功能失衡可能与rhBMP-2协同作用,导致MHD后免疫介导的心血管并发症高发。

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