外周血调节性T细胞及炎性因子表达与急性脑梗死TOAST亚型及脑梗死后感染风险的关系研究

Correlations of expressions of peripheral blood regulatory T cells and related inflammatory factors with TOAST subtypes and infection risk in patients with acute cerebral infarction

目的探讨不同TOAST亚型急性脑梗死患者免疫炎症反应程度的差异及其与脑梗死后感染风险的关系。方法对淮南市第一人民医院神经内科自2017年10月至2018年6月收治的154例入院时未发生感染的急性脑梗死患者(病例组)依据TOAST病因学分型分组,其中大动脉粥样硬化型组72例、心源性栓塞型组38例、小动脉闭塞型组44例,同时选取45例同期体检健康者作为对照组。于入院后第2天采集病例组新鲜血标本(对照组于体检时采集),采用流式细胞仪检测外周血CD4+CD25+CD127(low)调节性T细胞(Treg)占CD4+淋巴细胞的百分比(Treg%),采用酶联免疫吸附法或免疫散射比浊法检测白介素(IL)-6、IL-10、超敏C反应蛋白(hsCRP)水平。采用Spearman相关性分析检测Treg%及炎性因子与急性脑梗死TOAST亚型、脑梗死后感染的相关性,采用受试者工作特征(ROC)曲线分析Treg%及炎性因子对脑梗死后感染的预测价值,采用单因素Logistic回归分析及多因素Logistic回归分析筛选脑梗死后感染的危险因素。结果(1)大动脉粥样硬化型组Treg%明显低于对照组,心源性栓塞型组Treg%明显高于对照组,差异均有统计学意义(P<0.05);大动脉粥样硬化型组、心源性栓塞型组IL-6、hsCRP水平较对照组明显升高,大动脉粥样硬化型组、心源性栓塞型组、小动脉闭塞型组IL-10水平较对照组明显降低,差异均有统计学意义(P<0.05);大动脉粥样硬化型组、小动脉闭塞型组IL-6、IL-10水平较心源性栓塞型组明显降低,小动脉闭塞型组hsCRP水平较心源性栓塞型组明显降低,差异均有统计学意义(P<0.05)。Spearman相关性分析显示Treg%与大动脉粥样硬化型呈负相关关系(rs=-0.488,P=0.000),与心源性栓塞型及小动脉闭塞型呈正相关关系(rs=0.355,P=0.000;rs=0.200,P=0.013);IL-6、IL-10、hsCRP水平与心源性栓塞型呈正相关关系(rs=0.578,P=0.000;rs=0.508,P=0.000;rs=0.299,P=0.015),与小动脉闭塞型呈负相关关系(rs=-0.404,P=0.001;rs=-0.394,P=0.001;rs=-0.308,P=0.012)。(2)病例组中36例患者发生脑梗死后感染,脑梗死后感染患者与未感染患者相比Treg%及IL-6、IL-10、hsCRP水平均明显增高,差异均有统计学意义(P<0.05)。Spearman相关性分析显示Treg%、hsCRP与脑梗死后感染呈正相关关系(rs=0.305,P=0.007;rs=0.653,P=0.000)。ROC曲线分析显示hsCRP预测脑梗死后感染的曲线下面积为0.943(95%CI:0.895~0.992,P=0.000),Treg%预测脑梗死后感染的曲线下面积为0.707(95%CI:0.548~0.866,P=0.008),Treg%联合hsCRP预测脑梗死后感染的曲线下面积为0.958(95%CI:0.918~0.998,P=0.000)。多因素Logistic回归分析发现hsCRP为脑梗死后感染的独立危险因素(P<0.05)。结论不同TOAST亚型急性脑梗死患者间免疫炎症反应程度存在差异。Treg%及hsCRP可作为脑梗死后感染的早期预警标志物。

Objective To explore the differences of degrees of immune inflammatory response in patients with different TOAST subtypes of acute cerebral infarction and their relations with infection risk after cerebral infarction.Methods One hundred and fifty-four patients with acute cerebral infarction who were free of detectable infection on admission,admitted to our hospital from October 2017 to June 2018,were recruited as patient group;according to TOAST subtypes,these patients were divided into large-artery atherosclerosis group(LAA,n=72),cardioembolic group(CE,n=38),and small-artery occlusion group(SAO,n=44);45 healthy subjects enrolled at the same period were selected as control group.Fasting blood samples were taken on the next day of admission or during physical examination.Treg%(percentage of CD4+CD25+CD127[low]regulatory T cells[Treg]in CD4+lymphocytes)was measured by flow cytometry.Interleukin(IL)-6,IL-10,and hypersensitive C-reactive protein(hsCRP)levels were measured by ELISA or Turbidimetric inhibition immuno assay.Spearman correlation analysis was performed to investigate the relations of Treg%and related inflammatory factors with TOAST subtypes of acute cerebral infarction and post-stroke infection risk.Receiver operating characteristic(ROC)curve was used to analyze the predictive values of Treg%and inflammatory factors in post-stroke infection.Univariate Logistic regression analysis and multivariate Logistic regression analysis were used to screen the risk factors of infection after cerebral infarction.Results(1)Treg%in LAA group was significantly lower than that in control group(P<0.05),and Treg%in CE group was statistically higher than that in control group(P<0.05);patients in the LAA and CE groups had significantly higher IL-6 and hsCRP levels as compared with those in the control group(P<0.05);patients in the LAA,CE and SAO groups had significantly lower IL-10 level than those in the control group(P<0.05);patients in the LAA and SAO groups had significantly decreased IL-6 and IL-10 levels as compared with those in the CE group(P<0.05);patients in the SAO group had significantly lower hsCRP level as compared with those in the CE group(P<0.05).Spearman correlation analysis showed that Treg%was negatively correlated with LAA(rs=-0.488,P=0.000)and positively correlated with CE and SAO(rs=0.355,P=0.000;rs=0.200,P=0.013);the levels of IL-6,IL-10 and hsCRP were positively correlated with CE(rs=0.578,P=0.000;rs=0.508,P=0.000;rs=0.299,P=0.015),and negatively correlated with SAO(rs=-0.404,P=0.001;rs=0.394,P=0.001;rs=0.308,P=0.012).(2)There were 36 patients who developed infection associated with cerebral infarction in the patient group;as compared with those in the non-infection group,Treg%,IL-6,IL-10 and hsCRP levels in the infection group were significantly increased(P<0.05);Spearman correlation analysis showed that Treg%and hsCRP were positively correlated with infection after cerebral infarction(rs=0.305,P=0.007;rs=0.653,P=0.000).The area under the curve of hsCRP for prediction of post-stroke infection was 0.943(95%confidence interval[CI]:0.895-0.992,P=0.000),that of Treg%was 0.707(95%CI:0.548-0.866,P=0.008),and that of combination of hsCRP and Treg%was 0.958(95%CI:0.918-0.998,P=0.000).(3)Multivariate Logistic regression analysis showed that hsCRP was an independent risk factor for post-infarction infection(P<0.05).Conclusions There are differences in the degrees of immune inflammatory response among patients with different TOAST subtypes of acute cerebral infarction.Treg%and hsCRP can be used as early warning markers of infection after cerebral infarction.