衰老成血管T细胞与高血压患者血管内皮功能障碍及炎症状态的相关性  

Correlation between senescent angioblasts T cells and endothelial dysfunction and inflammatory in hypertensive patients

作　　者：夏文豪[1,2,3] 董兵 刘晓玲 何江 陶军[1,2,3] XIA Wen-hao;DONG Bin;LIU Xiao-ling;HE Jiang;TAO Jun(Department of Hypertension and Vascular Disease,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510000,China;Key Laboratory on Assisted Circulation,Ministry of Health;National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases)

机构地区：[1]中山大学附属第一医院高血压血管病科,广东广州510000 [2]国家卫生健康委员会辅助循环重点实验室 [3]血管疾病诊治技术国家地方联合工程实验室

出　　处：《中华高血压杂志》2021年第10期972-980,共9页Chinese Journal of Hypertension

基　　金：国家自然科学基金(82000461,81671379);中国博士后科学研究基金(2019M663309)。

摘　　要：目的探讨高血压患者成血管T(T_(ang))细胞的水平及其免疫衰老状态和促炎能力与内皮功能障碍及全身炎症状态的相关性。方法连续纳入2019年9月-2020年3月于中山大学附属第一医院高血压血管病科因高血压住院、未经降压治疗的原发性高血压患者120例,通过血流介导的肱动脉舒张功能(FMD)评估血管内皮功能,根据FMD≤7%和>7%将入组的高血压患者分为合并和不合并血管内皮功能障碍两组。流式细胞技术检测患者外周血T_(ang)细胞[CD3^(+)CD31^(+)CXC趋化因子受体-4(CXCR4)^(+)]CD4^(+)/CD8^(+)亚群中CD28^(null)和CD28^(+)细胞比例、细胞内γ-干扰素(IFN-γ),肿瘤坏死因子α(TNF-α),白细胞介素6(IL-6)和白细胞介素10(IL-10)的阳性率及衰老标志物CD57、CD27、趋化因子受体7(CCR7)和人端粒酶逆转录酶(hTERT)的表达。采用酶联免疫吸附试验(ELISA)法检测患者血清中炎症因子IL-6、IL-17、IFN-γ和TNF-α的水平,比较两组患者一般资料、血生化指标、T_(ang)细胞亚群、血清炎症因子的差异,Pearson相关分析T_(ang)细胞亚群与FMD和血清炎症因子的相关性,采用多元logistic回归和受试者工作特征曲线分析T_(ang)细胞亚群对血管内皮功能障碍的影响和诊断效能。结果高血压伴内皮功能障碍患者CD4^(+)T_(ang)细胞中CD28^(null)亚群比例显著升高,与FMD呈负相关(r=-0.643,P<0.01)。多元logistic回归分析显示,CD28^(null)CD4^(+)T_(ang)细胞比例升高是内皮功能障碍的影响因素(OR=3.428,95%CI 1.423~5.012,P<0.001),对内皮功能障碍具有良好的诊断效能(曲线下面积=0.885,P<0.001)。免疫分型显示,CD28^(null)CD4^(+)T_(ang)的CD57表达升高,而CCR7、CD27及hTERT表达下降,呈现衰老特征,同时细胞内IL-6、IFN-γ和TNF-α阳性比例升高。CD28^(null)CD4^(+)T_(ang)细胞数与高血压患者血清中IL-6、IL-17、IFN-γ和TNF-α水平显著相关。结论具有衰老和促炎表型的CD28^(null)CD4^(+)T_(ang)细胞亚群�Objective To explore the association of the levels of angiogenic T(T_(ang))cells and immunologic senescence,pro-inflammatory capacity of these cells with endothelial dysfunction and systemic inflammation in hypertensive patients.Methods A total of 120 untreated inpatients with essential hypertension from the Department of Hypertension and Vascular Disease in the First Affiliated Hospital of Sun Yat-sen University were enrolled from September 2019 to March 2020.Flow-mediated dilation(FMD)of brachial artery was used to evaluate endothelial function.Based on FMD≤7%and>7%,patients were divided into two groups according to the presence and absence of vascular endothelial dysfunction.Proportion of CD28^(null)andCD28^(+)in CD4^(+)/CD8^(+)subset of T_(ang)cells[CD3^(+)CD31^(+)CXC chemokine receptor-4(CXCR4)^(+)]in peripheral blood andγ-interferon(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-10(IL-10)positive cells,and the expression of CD57,CD27(serve as senescent profiles),CC-chemokine receptor 7(CCR7)and human telomerase reverse transcriptase(hTERT)were measured by flow cytometry.Levels of serum cytokines including IL-6,interleukin-17(IL-17),IFN-γ,TNF-αwere detected by enzyme-linked immunosorbent assay(ELISA).The baseline data,biochemical indicators,T_(ang)cells subsets,and serum inflammatory differences of two groups were compared.Pearson correlation analysis were used to analyze the correlation between the subset of CD28^(null)CD4^(+)T_(ang)cells and FMD,serum cytokines.Logistic regression and receiver operating characteristic(ROC)curve were used to determine the association and diagnostic efficacy of T_(ang)cell subsets for endothelial dysfunction.Results The proportion of CD28^(null)subset was significantly higher in CD4^(+)T_(ang)cells in hypertensive patients with endothelial dysfunction,which was negatively correlated with FMD(r=-0.643,P<0.01).Multiple logistic regression analysis showed that higher proportion of CD28^(null)CD4^(+)T_(ang)cells was associated with endothelial dysf

关 键 词：高血压 内皮功能障碍 成血管T细胞 炎症 免疫衰老 

分 类 号：R544.1[医药卫生—心血管疾病]