不同程度颈动脉粥样硬化老年患者T淋巴细胞分化亚群、炎症水平与血管内皮功能关联性分析

Association of T lymphocyte differentiation subgroups and inflammation levels with vascular endothelial function in elderly patients with different degrees of carotid atherosclerosis

目的探讨不同程度颈动脉粥样硬化患者T淋巴细胞分化亚群及炎症水平与血管内皮功能的相关性。方法我院于2017年1月至2018年12月期间收治的180例颈动脉粥样硬化患者作为研究对象,根据颈动脉粥样硬化的梗死体积分为高、中、低3组(58例、60例、62例),并以同期160例排除颈动脉粥样硬化者为对照组,采用流式细胞仪检测各组血清T细胞亚群(CD4+、CD8+)、Th1、Th2、Th17、Treg细胞水平;采取酶联免疫吸附测定(ELISA)法检测血清炎症因子(TNF-α、IL-6、IL-17)水平;另采用彩色多普勒超声检查仪检测各组患者肱动脉内皮依赖性功能(FMD)、非内皮依赖性功能(NMD)和颈动脉内膜中层厚度(IMT)等血管内皮功能参数。采用Pearson相关性分析Th17、Treg细胞亚群、炎症水平与血管内皮功能之间的相关性。结果动脉粥样硬化患者TNF-α、IL-6、IL-17表达水平显著高于健康对照者(P<0.05),且随着颈动脉粥样硬化的梗死体积增大,血清各炎症因子表达水平显著上升(P<0.05);颈动脉粥样硬化患者CD4+T细胞水平以及Th1、Th2、Th17细胞比例明显高于对照组(P<0.05),CD8+T细胞水平以及Treg细胞比例明显低于对照组(P<0.05),且随着颈动脉梗死程度增加,T细胞亚群和辅助性T细胞水平异常表达程度越高(P<0.05);动脉粥样硬化患者FMD、NMD明显低于对照组(P<0.05),IMT显著高于对照组(P<0.05)。且随着梗死程度增加,患者血管功能各指标明显下降(P<0.05);Pearson相关性分析结果表明,CD4+细胞水平、血清TNF-α表达水平以及Th17细胞比例与血管内皮功能指标FMD水平呈显著负相关(r分别为-0.902、-0.896、-0.865,P值均小于0.001),Treg细胞比例与FMD水平呈显著正相关(r=0.888,P<0.001)。结论老年颈动脉粥样硬化患者血管内皮功能下降,血清炎症因子、T淋巴细胞分化亚群表达水平均与健康人存在差异表达,且表达水平与患者严重程度以及血管内皮功能存在显著相关性。表明机体炎症和免疫反应机制参与颈动脉粥样硬化发生和发展,为颈动脉粥样硬化性免疫提供理论基础。

This study was designed to investigate the correlation of T lymphocyte differentiation subgroups and inflammation levels with vascular endothelial function in patients with different degrees of carotid atherosclerosis.Total of 180 patients with carotid atherosclerosis were enrolled and divided into high(58), middle(60) and low(60)groups, according to the infarct volume of carotid atherosclerosis, while 160 cases of carotid atherosclerosis were excluded as control group.Flow cytometry was used to detect serum T cell subgroups(CD4^+, CD8^+), Th1, Th2, Th17, and Treg cell levels in each group;ELISA was used to detect serum inflammatory factors(TNF-α, IL-6, IL-17) levels;color Doppler ultrasound was used to detect vascular endothelial function parameters such as brachial artery endothelium-dependent function(FMD), non-endothelial function(NMD) and carotid intima-media thickness(IMT).Then Pearson correlation was used to analyze the correlation of Th17, Treg cell subsets, inflammation level with vascular endothelial function.Data showed that the expression levels of TNF-α, IL-6 and IL-17 in atherosclerosis patients were significantly higher than those in controls(P<0.05), and with the increase of infarct volume of carotid atherosclerosis, the expression levels of serum inflammatory factors increased significantly(P<0.05).The levels of CD4^+T cells and Th1, Th2 and Th17 cells in patients with carotid atherosclerosis were significantly higher than those in controls(P<0.05), while the levels of CD8^+T cells and Treg cells were significantly lower than those in the control group(P<0.05).And with the increase of carotid artery infarction, the abnormal expression of T cell subsets and helper T cells were more worse(P<0.05).The FMD and NMD of patients with atherosclerosis were significantly lower than those of controls(P<0.05), and IMT was significantly higher than that of the control group(P<0.05).With the increase of infarction degree, the vascular function indexes of patients were significantly decreased(P<0.05).Pearson correlation analysis showed that CD4^+cell level, serum TNF-α expression level and Th17 cell ratio were negatively related with vascular endothelial function index FMD level(r=0.902,-0.996,-0.865, P<0.001), and the proportion of Treg cells was positively correlated with FMD level(r=0.888, P<0.001).Taken together, the vascular endothelial function of patients with carotid atherosclerosis is decreased, and the expression levels of serum inflammatory factors and T lymphocyte differentiation subpopulations are significantly correlated with the severity of patients with carotid atherosclerosis, which indicates the body inflammation and immune response are involved in the occurrence and development of carotid atherosclerosis, and provides a theoretical basis for carotid atherosclerotic immunity.