伴颈动脉粥样硬化脑梗患者CD4+CD28null T细胞CD158j表达和ERK磷酸化水平的关系

摘要

目的 探讨伴颈动脉粥样硬化(CA)脑梗患者CD4+CD28null T细胞上CD158j的表达百分率和ERK磷酸化(p-ERK)水平的关系及对颈动脉粥样斑块不稳定的影响.方法 采用流式细胞术检测106例伴CA脑梗、33例颈动脉正常脑梗患者和50例健康人外周血CD4+CD28null T细胞数量,以及CD4+CD28null T细胞CD158j和穿孔素(perforin)的表达,36例斑块不稳定患者CD4+T细胞p-ERK水平.ELISA法检测血清IFN-γ水平.B超检查以上人群颈动脉血管内壁粥样硬化情况.结果 脑梗患者CD4+CD28nullT细胞数量、CD4+CD28null T细胞CD158j和perforin的表达,以及血清IFN-γ水平,均明显高于健康对照组(P均<0.01);CD4+CD28null T细胞数量、CD4+CD28null T细胞CD158j和perforin的表达,以及血清IFN-γ水平,在脑梗患者中由高到低依次为颈动脉不稳定斑块组、颈动脉稳定斑块组、颈动脉内-中膜厚度(IMT)增厚组和颈动脉正常组.颈动脉不稳定斑块脑梗患者CD4+CD28null T细胞CD158j的表达与p-ERK水平呈显著性正相关(P<0.01).结论 伴CA脑梗患者CD4+CD28null T细胞数量明显增多.CD158j可能通过上调p-ERK水平,促进CD4+CD28null淋巴细胞增殖,产生细胞毒效应和分泌细胞因子,最终导致颈动脉粥样斑块不稳定.%Objective To investigate the relationship between CD158j expression and phosphorylated ERK (p-ERK) in CD4+ CD28null T cells in cerebral infarction (CI) patients- with carotid atherosclerosis and its effects on carotid atherosclerotic plaque stability. Methods Percentage of peripheral CD4+ CD28null and the expression of CD158j and perform on CD4+ CD28null cells was analyzed with flow cytometry in 106 CI patients with carotid atherosclerosis, 33 CI patients with normal carotid arteries and in 50 normal controls, respectively; p-ERK expression was assayed with flow cytometry in 36 CI patients with unstable plaque, and serum IFN-γ was detected with ELISA. The intima-media thickness (IMT) of bilateral carotid arteries in all subjects was confirmed by the colour Doppler ultrasonograph imagingResults Percentage of the CD4+ CD28null T cells, expression of CD158j and perform on CD4+ CD28null T cells and the serum IFN-γ levels was dramatically higher in CI patients than that in normal controls, respectively (all P <0.01), which was decreased in an order of CI patients with patients with unstable plaque, stable plaque, carotid artery IMT and with normal carotid artery. A strong positive correlation was observed between the CD158j expression and degree of p-ERK in CI patients with unstable plaque (P < 0. 01). Conclusion CD4+ CD28null T cells were significantly increased in CI patients with carotid atherosclerosis. CD158j might up-regulate p-ERK expression and induce the proliferation of the CD4+ CD28nullT cells; consequently, higher cytokine production such as IFN-γ produced by CD4+ CD28null T cells may cause the formation of unstable plaque.