天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (4): 416-418.doi: 10.11958/j.issn.0253-9896.2015.04.022

• 专题研究·心血管疾病 • 上一篇    下一篇

急性冠脉综合征患者mTOR 活化与调节性T 细胞及细胞因子的关系

张艳1，2，李志樑1△，胡春玲2   

  1. 1南方医科大学附属珠江医院心内科，广东广州（邮编510282）；2广东省妇幼保健院内科
  • 收稿日期:2014-08-26 修回日期:2014-10-29 出版日期:2015-04-15 发布日期:2015-04-13
  • 通讯作者: 李志樑 E-mail:happydragon2012qq@126.com
  • 作者简介:张艳（1979），女，主治医师，博士在读，主要从事冠心病防治的研究

Relationship among mTOR levels，regulatory T cells and cytokins in patients with acute coronary syndrome

ZHANG Yan1，2, LI Zhiliang1△, HU Chunling2   

  1. 1 Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China；2 Department of Internal Medicine, Guangdong Province Maternity and Child Care Hospital
  • Received:2014-08-26 Revised:2014-10-29 Published:2015-04-15 Online:2015-04-13
  • Contact: LI Zhiliang E-mail:happydragon2012qq@126.com

PDF (PC)

4227

摘要： 摘要：目的检测哺乳动物雷帕霉素靶蛋白（mTOR）在急性冠脉综合征（ACS）患者外周血T 细胞中的活化状态，及其与调节性T 细胞（Tregs）以及细胞因子的关系。方法选取ACS 患者32 例（ACS 组），同期因胸痛症状为主诉但心电图及冠脉造影正常，排除冠心病的胸痛综合征（CPS）患者28 例为对照组；采用蛋白免疫印迹法检测2 组外周血T 细胞中mTOR、p70S6KT389 磷酸化（p-p70S6KT389）及AKTS473 磷酸化（p-AKTS473）水平；酶联免疫吸附测定法测T 细胞亚群相关细胞因子干扰素-γ（IFN-γ）、白细胞介素（IL）-4、IL-17 及转化生长因子-β1（TGF-β1）水平；流式细胞仪检测CD4+CD25+FoxP3+Tregs 占CD4+T 细胞的百分比；采用Spearman 相关分析各指标之间的关联性。结果ACS 组mTOR 及p-p70S6KT389 表达量均高于对照组(均P＜0.01)；与对照组比较，ACS 组IFN-γ、IL-17 升高，Tregs 百分比及TGF-β1 减少(均P＜0.05)，而2 组p-AKTS473、IL-4 比较差异无统计学意义；相关分析显示p-p70S6KT389 与IFN-γ及 IL-17 呈显著正相关（rs 分别为0.91，0.92，均P＜0.01），与Tregs 及TGF-β1 呈显著负相关（rs 分别为-0.85，-0.80，均 P＜0.01）。结论ACS 患者外周血T 细胞中mTORC1 活化与Tregs 减少及细胞因子失衡有关。

关键词: 急性冠脉综合征, 他克莫司结合蛋白质类, T 淋巴细胞, 调节性, 细胞因子类, 哺乳动物雷帕霉素靶蛋白

Abstract: Abstract：Objective To assess whether mTOR was activated in peripheral T lymphocytes of acute coronary syndrome （ACS）patients and to investigate the relationship among mTOR，regulatory T cells and cytokins. Methods Patients with acute coronary syndrome (n=32) were selected in ACS group. Meanwhile, patients who complainted of chest pain but were proven to be normal in ECG and in coronary arteriography, were excluded as ACS patients but were diagnosed as Chest Pain Syndrome (CPS) and selected in CPS group (n=28). The expression levels of mTOR, phospho- p70S6KT389 (indicative of mTORC1 activity) and phospho-AKTS473(indicative of mTORC2 activity) were investigated in T cells, which were isolated from peripheral blood of patients in ACS group or CPS group, using Western blot. The proportion of CD4+CD25+Foxp3+Tregs over CD4+ cells were evaluated by FACS. And T cell subset related cytokines such as IFN-γ, IL-4, IL-17 and TGF-β1 were exam⁃ ined by ELISA. Then we investigated the relationship among mTOR，regulatory T cells and cytokins by Spearman analysis. Results mTOR and p-p70S6KT389 expression were significantly enhanced in ACS group as compared with those in patients from CPS group (P＜0.01). Higher levels of IFN-γ, IL-17 but lower level of TGF-β1 cytokines as well as decreased propor⁃ tion of Tregs were observed in ACS group than those in CPS group (P＜0.05). There was no significant difference in the level of IL-4 and p-AKTS473 between the two groups (P＞0.05). By correlation analysis, p-p70S6KT389 expression level positively correlated with IFN-γ, IL-17（rs=0.91,092，P＜0.01）and negatively correlated with Tregs and TGF-β1 （rs=-0.85,-0.80, re⁃ spectively, P＜0.01）. Conclusion mTORC1 pathway was activated in peripheral T lymphocytes of ACS patients, and Tregs insufficiency and cytokins imbalance both contribute to the activation of mTORC1 pathway and pathological process of ACS.

Key words: acute coronary syndrome, tacrolimus binding proteins；T-lymphocytes, regulatory；cytokines；mTOR