维持性血液透析患者外周血辅助性T细胞17／调节性T细胞失衡与动脉粥样硬化心血管疾病的关系  

Relationship between T- helper cell 17/regulatory T cell imbalance and atherosclerosis cardiovascular disease in maintenance hemodialysis patients

作　　者：马妹琛 刘峰[1] 王奕[1] 王俊[1] 李晓珺[1] 江薇[1] 庄守纲[1] 严海东[1] 齐华林[1] 

机构地区：[1]上海市东方医院(同济大学附属东方医院)肾内科,200120

出　　处：《中华肾脏病杂志》2016年第2期118-125,共8页Chinese Journal of Nephrology

基　　金：2011年上海市浦东新区科技发展基金创新资金（PKJ2011-Y04）

摘　　要：目的探讨维持性血液透析（MHD）患者外周血辅助性T细胞17（Thl7）／调节性T细胞（Treg）是否存在比例、功能失衡以及与动脉粥样硬化心血管疾病（ASCVD）的关系。方法入选57例MHD患者（其中ASCVD患者25例，无ASCVD患者32例）和24例健康对照组。采用颈动脉超声测定颈动脉中．内膜厚度（CCA—IMT）、颈动脉斑块及斑块面积；流式细胞术检测外周血Treg细胞（CD4^＋CD25^＋Foxp3^＋）和Thl7细胞（CD4^＋IL-17^＋）；实时定量PCR检测Foxp3和视黄酸相关的孤儿受体γt（RORγt）mRNA表达；ELISA检测血清中TGF-β1、白细胞介素（IL）-10、IL-17、IL-6表达水平。结果MHD合并ASCVD患者的Treg细胞比例、Foxp3mRNA水平及相关细胞因子TGF-β1、IL-10水平均显著低于无ASCVD患者和健康对照组（均P〈0．01），而其Thl7细胞比例、RORγtmRNA及IL—17、IL-6水平、Thl7／Treg比值均显著高于无ASCVD患者和健康对照组（均P〈0．01）。相关性分析显示，Treg细胞比例与CCA—IMT无相关，但IL-10水平与CCA-IMT呈负相关（P〈0．05）；Thl7细胞比例、IL-17水平、Thl7／Treg比值与CCA-IMT呈正相关（均P〈0．05）。斑块组患者Treg细胞比例及TGF-β1、IL-10水平显著低于无斑块组，Thl7细胞比例、IL-17水平、Thl7／Treg比值均显著高于无斑块组（均P〈0．05）。且斑块组中Treg细胞比例与斑块面积呈负相关（P〈0．01）。结论MHD患者存在Thl7／Treg数量、功能失衡，尤其在合并ASCVD的患者中更显著，且与微炎性反应、动脉粥样硬化等密切相关，可能在ASCVD的发生发展过程中起重要作用。Objective To investigate whether the T-helper cell 17 （Thl7）/regulatory T cell （Treg） of patients on maintenance hemodialysis （MHD） present imbalance in terms of proportion and function, and if so, the relationship between such imbalance and atherosclerosis cardiovascular disease （ASCVD）. Methods Fifty-seven MHD patients, included 25 with ASCVD and 32 without ASCVD, and 24 healthy volunteers were enrolled. The common carotid artery intima media thickness （CCA-IMT）, carotid plaque and plaque area were determined with high-resolution B-mode ultrasonography. Treg （CD4＋ CD25＋Foxp3~） and Thl7 （CD4＋IL-17＋） were measured by flow cytometry. The Foxp3 ＋and RAR-related orphan receptor γt （RORγt） mRNA expressions were measured by real-time PCR. TGF-131, IL-10, IL-17and IL-6 in serum were detected by ELISA. Results There were decreased Treg proportion, Foxp3 mRNA, TGF-131 and IL-10, and increased Thl7 proportion, RORTt mRNA, IL-17, IL-6 and Thl7/ Treg in the ASCVD group compared with that in the non-ASCVD group and healthy group （all P 〈 0.01）. No correlation was observed between Treg and CCA-IMT, but IL-10 were negatively correlated with CCA-IMT （P 〈 0.05）. Thl7, IL-17 and ratio of Thl7/Treg were positively correlated with CCA- IMT （all P 〈 0.05）. MHD patients with carotid plaques had lower Treg, TGF- [31 and IL- 10, higher Thl7, IL- 17 and ratio of Thl7/Treg than those without carotid plaques （all P 〈 0.05）. Moreover, Treg proportion was negatively correlated with carotid plaque area in MHD patients with carotid plaques （P〈 0.01）. Conclusions The Thl7/Treg numerical and functional imbalance exists in MHD patients, especially in patients with ASCVD. This might act synergistically with micro-inflammation on immune-mediated atherosclerosis and contribute to the high incidence of ASCVD.

关 键 词：肾透析 T淋巴细胞 调节性 T淋巴细胞 辅助诱导 心血管疾病 

分 类 号：R459.5[医药卫生—治疗学]