2型糖尿病合并颈动脉粥样硬化患者外周血T淋巴细胞和相关细胞因子的变化及研究

Changes of peripheral blood T cell subsets and related cytokines in patients with type 2 diabetes mellitus and carotid atherosclerosis

目的探讨2型糖尿病(type 2 diabetes mellitus, T2DM)合并颈动脉粥样硬化(carotid atherosclerosis, CAS)患者外周血T淋巴细胞比率、相关细胞因子表达及其与颈动脉内膜中层厚度(intima-media thickness, IMT)和糖化血红蛋白(glycosylated hemoglobin, HbA1c)的相关性。方法 80例T2DM患者,其中有CAS斑块者40例为CAS组,无CAS斑块者40例为无CAS组;体检健康者40例为对照组。3组采用流式细胞仪测定外周血Th1、Th2、Th17及Treg细胞比例,采用ELISA法检测血清白细胞介素(interleukin, IL)-2、IL-4、IL-6、IL-10、IL-17、干扰素(interferon, IFN)-γ水平,并测量IMT和HbA1c水平,分析外周血T淋巴细胞与IMT和HbA1c的相关性。结果 CAS组Th1细胞和Th17细胞百分率[(19.47±2.45)%、(2.34±0.33)%]及IL-2[(211.24±31.49)ng/L]、IL-17[(19.54±3.27)ng/L]、IFN-γ[(19.72±3.21)ng/L]水平、HbA1c[(11.28±1.56)%]、IMT[(1.45±0.40)mm]明显高于无CAS组[(15.24±1.62)%、(1.50±0.28)%、(184.32±25.74)ng/L、(15.76±2.08)ng/L、(15.68±2.07)ng/L、(8.92±1.09)%、(1.01±0.27)mm]和对照组[(10.02±1.14)%、(0.96±0.25)%、(128.46±17.49)ng/L、(7.32±0.99)ng/L、(10.43±1.21)ng/L、(5.22±0.84)%、(0.76±0.13)mm](P<0.05),无CAS组高于对照组(P<0.05);CAS组Th2细胞和Treg细胞百分率[(2.25±0.49)%、(4.03±0.75)%]及IL-4[(4.72±0.32)ng/L]、IL-6[(11.21±1.04)ng/L]、IL-10[(11.07±1.27)ng/L]水平低于无CAS组[(2.97±0.67)%、(5.67±1.33)%、(5.36±0.61)ng/L、(13.24±1.96)ng/L、(14.77±1.93)ng/L]和对照组[(3.36±0.83)%、(6.57±1.52)%、(7.32±0.95)ng/L、(17.75±2.36)ng/L、(22.72±2.59)ng/L](P<0.05),无CAS组低于对照组(P<0.05);CAS组患者IMT与Th1、Th17细胞水平呈正相关(r=0.809,P<0.001;r=0.648,P<0.001),与Th2、Treg细胞水平呈负相关(r=-0.580,P<0.001;r=-0.643,P<0.001),HbA1c与Th1、Th17细胞水平呈正相关(r=0.601,P<0.001;r=0.528,P<0.001),与Th2、Treg细胞水平呈负相关(r=-0.844,P<0.001;r=-0.602,P<0.001)。结论糖尿病合并CAS患者存在Th1、Th17细胞比率上调,Th2、Treg细胞比率下调,IL-2、IL-17、IFN-γ分泌增多,IL-4、-6、-10分泌减少,且与患者疾病进展程度相关。

Objective To investigate the percentages of peripheral blood T cell subsets and the expressions of related cytokines in patients with type 2 diabetes mellitus(T2 DM) and carotid atherosclerosis(CAS) and their correlations with the carotid intima-media thickness(IMT) and glycosylated hemoglobin(HbA1c) level. Methods Eighty patients with T2 DM were divided into CAS plague group and non-CAS plaque group, with 40 patients in each group, and another 40 healthy volunteers were as controls(control group). The percentages of Th1, Th2, Th17 and Treg cells were detected by flow cytometry. The levels of interleukin(IL)-2, IL-4, IL-6, IL-10, IL-17 and interferon(IFN)-γ were detected by ELISA technique. The IMT was measured and HbA1c was detected. The correlations of peripheral blood T cell subsets with IMT and HbA1c were analyzed. Results The percentages of Th1 and Th17 cells((19.47±2.45)%,(2.34±0.33)%), the levels of IL-2((211.24±31.49) ng/L), IL-17((19.54±3.27) ng/L), IFN-γ((19.72±3.21) ng/L) and HbA1c((11.28±1.56)%) as well as IMT((1.45±0.40) mm) in CAS plaque group were significantly higher than those in non-CAS plaque group((15.24±1.62)%,(1.50±0.28)%,(184.32±25.74)ng/L,(15.76±2.08)ng/L,(15.68±2.07)ng/L,(8.92±1.09)%,(1.01±0.27)mm)and control group((10.02±1.14)%,(0.96±0.25)%,(128.46±17.49)ng/L,(7.32±0.99)ng/L,(10.43±1.21)ng/L,(5.22±0.84)%,(0.76±0.13)mm)(P<0.05),and higher in non-CAS plaque group than those in control group(P<0.05).The percentages of Th2 and Treg cells((2.25±0.49)%,(4.03±0.75)%)and the levels of IL-4,IL-6 and IL-10((4.72±0.32),(11.21±1.04),(11.07±1.27)ng/L)in CAS plaque group were significantly lower than those in non-CAS plaque group((2.97±0.67)%,(5.67±1.33)%,(5.36±0.61)ng/L,(13.24±1.96)ng/L,(14.77±1.93)ng/L)and control group((3.36±0.83)%,(6.57±1.52)%,(7.32±0.95)ng/L,(17.75±2.36)ng/L,(22.72±2.59)ng/L)(P<0.05),and lower in non-CAS plaque group than those in control group(P<0.05).In CAS plaque group,IMT was positively correlated with the levels of Th1 and Th17 cells(r=0.809,P0.001;r=0.648,P<0.001),and negatively correlated with the levels of Th2 and Treg cells(r=-0.580,P0.001;r=-0.643,P<0.001);HbA1 c was positively correlated with the levels of Th1 and Th17 cells(r=0.601,P0.001;r=0.528,P<0.001),and negatively correlated with the levels of Th2 and Treg cells(r=-0.844,P0.001;r=-0.602,P<0.001).Conclusion The percentages of Th1 and Th17 cells are up-regulated,the percentages of Th2 and Treg cells are down-regulated,the levels of IL-2,IL-17 and IFN-γincrease,and the levels of IL-4,IL-6 and IL-10 decrease,which are correlated with the severity of disease.