不同血糖水平的冠心病患者外周血中Th1、Th2细胞比例变化分析

Changes of Th1 and Th2 Cell Ratio in Peripheral Blood of Patients with Coronary Heart Disease at Different Blood Glucose Levels

目的探讨不同血糖水平的冠心病患者外周血中1型辅助性T细胞(Th1)、2型辅助性T细胞(Th2)的细胞比例变化.方法选取冠心病患者86例,根据血糖检测结果分为冠心病血糖正常组34例,冠心病合并糖耐量异常组20例,冠心病合并糖尿病组32例;另收集同期健康志愿者25名为健康对照组.采集空腹外周静脉血,检测空腹血糖、糖化血红蛋白、γ干扰素、白细胞介素4、白细胞介素5、白细胞介素10水平.分离外周血单个核细胞,流式细胞仪检测Th1、Th2细胞比例.分离并培养人脐静脉内皮细胞,并使用免疫磁珠清除外周血单个核细胞中CD4+T细胞,进行人脐静脉内皮细胞毒性试验.出院后对冠心病患者进行1 a的随访,记录主要不良心血管事件发生情况.结果冠心病合并糖尿病组患者空腹血糖、糖化血红蛋白水平明显高于健康对照组、冠心病血糖正常组、冠心病合并糖耐量异常组(P<0.05).冠心病合并糖尿病组Th1细胞比例明显高于冠心病合并糖耐量异常组、冠心病血糖正常组、健康对照组,Th2细胞比例明显低于冠心病合并糖耐量异常组、冠心病血糖正常组、健康对照组(P<0.05).冠心病合并糖尿病组γ干扰素水平明显高于冠心病合并糖耐量异常组、冠心病血糖正常组、健康对照组,白细胞介素4、白细胞介素5、白细胞介素10水平明显低于冠心病合并糖耐量异常组、冠心病血糖正常组、健康对照组(P<0.05).冠心病合并糖尿病组患者外周血单个核细胞水平明显低于冠心病合并糖耐量异常组、冠心病血糖正常组、健康对照组(P<0.05);清除CD4+T细胞的外周血单个核细胞在各组间比较差异无统计学意义(P>0.05).空腹血糖、糖化血红蛋白、Th1细胞比例、Th2细胞比例对冠心病患者预后均具有较高的预测价值(P<0.05);其中各指标联合检测的预测价值最高(AUC=0.942),灵敏度、阳性预测值均明显高于各指标单独检测.结论高糖状态下冠心病患者外周血中Th1细胞比例升高,Th2细胞比例降低,能够加速血管内皮细胞损伤,与空腹血糖和糖化血红蛋白联合检测可用于患者预后评估.

Objective To investigate the changes of the proportion of type 1 helper T cells(Th1)and type 2 helper T cells(Th2)in peripheral blood of patients with coronary heart disease(CHD)at different blood glucose levels.Method 86 patients with coronary heart disease were selected and divided into normal blood glucose with 34 patients,coronary heart disease complicated with abnormal glucose tolerance with 20 patients,and coronary heart disease complicated with diabetes with 32 patients according to the blood glucose test results;Another 25 healthy volunteers in the same period were collected as healthy control group.Collect fasting peripheral venous blood to detect fasting blood glucose,glycosylated hemoglobin the levels of interferonγ,interleukin 4,interleukin 5 and interleukin 10.The peripheral blood mononuclear cells were isolated and the ratio of Th1 and Th2 cells was detected by flow cytometry.Human umbilical vein endothelial cells were isolated and cultured,and CD4+T cells in peripheral blood mononuclear cells were removed by immunomagnetic strain to carry out the toxicity test of human umbilical vein endothelial cells.After discharge,patients with coronary heart disease were followed up for 1 year to record the occurrence of major adverse cardiovascular events.Results The levels of fasting blood glucose and glycosylated hemoglobin in patients with coronary heart disease and diabetes were significantly higher than those in healthy control group,coronary heart disease with normal blood glucose group and coronary heart disease with abnormal glucose tolerance group(P<0.05).The proportion of Th1 cells in coronary heart disease with diabetes was significantly higher than that in coronary heart disease with abnormal glucose tolerance,coronary heart disease with normal blood glucose,and healthy control group,while the proportion of Th2 cells was significantly lower than that in coronary heart disease group with abnormal glucose tolerance,group in coronary heart disease with normal blood glucose,and healthy control group,with statistical significance(P<0.05).The level of interferonγin coronary heart disease with diabetes group was significantly higher than that of coronary heart disease combined with abnormal glucose tolerance group,coronary heart disease with normal blood glucose group and healthy control group,and the levels of IL-4,IL-5 and IL-10 were significantly lower than that of coronary heart disease combined with abnormal glucose tolerance group,coronary heart disease with normal blood glucose group and healthy control group,with significant difference(P<0.05).The level of peripheral blood mononuclear cells in coronary heart disease and diabetes group was significantly lower than that in coronary heart disease and abnormal glucose tolerance group,coronary heart disease and normal blood glucose group,and healthy control group(P<0.05);There was no significant difference in peripheral blood mononuclear cells that cleared CD4+T cells among the groups(P>0.05).Fasting blood glucose,glycosylated hemoglobin,Th1 cell ratio and Th2 cell ratio have high predictive value for the prognosis of patients with coronary heart disease(P<0.05);Among them,the predictive value of combined detection of all indicators is the highest(AUC=0.942),and the sensitivity and positive predictive values are significantly higher than those of individual detection of all indicators.Conclusion Under the condition of high glucose,the proportion of Th1 cells in peripheral blood of patients with coronary heart disease increases and the proportion of Th2 cells decreases,which accelerates the injury of vascular endothelial cells.The combined detection with fasting blood glucose and glycosylated hemoglobin can be used to evaluate the prognosis of patients.