白细胞介素-7增强脓毒性心肌病患者辅助性T细胞9活性  

Interleukin-7 enhances T helper 9 cell activity in patients with septic cardiomypathy

作　　者：张宇[1] 厉菁[1] 张华[1] 张传西 Zhang Yu;Li Jing;Zhang Hua;Zhang Chuanxi(Department of Cardiovascular Medicine,The 7th People’s Hospital of Zhengzhou,Zhengzhou 450000,China)

机构地区：[1]郑州市第七人民医院心血管内科,郑州450000

出　　处：《中华急诊医学杂志》2024年第1期70-77,共8页Chinese Journal of Emergency Medicine

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20191112)。

摘　　要：目的观察白细胞介素-7(interleukin-7,IL-7)、辅助性T细胞9(T helper cell 9,Th9)、杀伤性T细胞9(cytotoxic T cell 9,Tc9)在脓毒性心肌病患者中的水平,评估外源性IL-7对脓毒性心肌病患者Th9细胞的调控。方法采用横断面研究,纳入2018年6月至2022年1月在郑州市第七人民医院就诊的脓毒性心肌病患者、脓毒症患者和对照者,分离血浆和外周血单个核细胞(peripheral blood mononuclear cells,PBMCs),重组IL-7刺激PBMCs,酶联免疫吸附试验检测IL-7、IL-9、可溶型CD127水平,流式细胞术检测T细胞中CD127表达和Th9、Tc9细胞比例,实时定量PCR法检测富含嘌呤的核酸结合蛋白1(purine-rich nucleic acid binding protein 1,PU.1)和转录因子叉头框蛋白O1(forkhead box protein O1,Foxo1)mRNA表达。重组IL-7刺激脓毒性心肌病患者分选的Th9细胞后与自体CD8+T细胞、人脐静脉内皮细胞共培养,检测靶细胞死亡、毒性分子和细胞因子的分泌。组间比较采用Kruskal-Wallis检验或Dunns多重检验,刺激前后比较采用配对t检验或Wilcoxon配对检验。结果纳入21例脓毒性心肌病患者、56例脓毒症患者、31例对照者。脓毒性心肌病患者IL-7水平低于脓毒症患者和对照者[75.71(42.28,135.59)pg/mL vs.118.47(60.18,171.73)pg/mL vs.168.42(105.41,232.30)pg/mL,P<0.05]。可溶型CD127在脓毒性心肌病患者和脓毒症患者的水平高于对照者[96.70(56.76,147.04)pg/mL vs.69.75(43.19,111.28)pg/mL vs.29.13(19.33,42.11)pg/mL,P<0.001]。CD127+CD8+细胞比例在三组之间的差异无统计学意义(P=0.477)。脓毒性心肌病患者Th9比例和Foxo1 mRNA表达低于脓毒症患者和对照者(P<0.001),脓毒性心肌病和脓毒症患者Tc9比例、PU.1 mRNA表达和IL-9水平均低于对照组(P<0.001)。脓毒性心肌病患者PBMCs经IL-7刺激后,Th9比例、PU.1和Foxo1 mRNA表达、IL-9分泌均高于无IL-7刺激(P<0.05)。脓毒性心肌病患者分选的Th9细胞经IL-7刺激后可促进自体CD8+T细胞介导的靶细胞死�Objective To investigate the levels of interleukin-7(IL-7),T helper cell 9(Th9),and cytotoxic T cell 9(Tc9),and to assess the regulation of exogenous IL-7 to Th9 in septic cardiomypathy patients.Methods A cross-sectional study was conducted.Septic cardiomypathy patients,septic patients,and controls were enrolled in the 7th People’s Hospital of Zhengzhou between June 2018 and January 2022.Plasma and peripheral blood mononuclear cells(PBMCs)were isolated.PBMCs were stimulated with recombinant IL-7.Plasma IL-7,IL-9,and soluble CD127 levels were measured by enzyme-linked immunosorbent assay.CD127 expression on T cells and Th9/Tc9 percentageswere measured by flow cytometry.mRNAexpressions of purine-rich nucleic acid binding protein 1(PU.1)and forkhead box protein O1(Foxo1)were semi-quantified by real-time PCR.IL-7-stimulated Th9 cells from septic cardiomypathy patients were co-cultured with autologous CD8+T cells and human umbilical vein endothelial cells.Target cell death,cytotoxic molecules and cytokines secretions were investigated.Kruskal-Wallis test was used for comparison among groups,while Dunns multiple test was used for comparison between the two groups.Paired t test or Wilcoxon paired test was used for comparison before and after stimulation.Results A total of 21 septic cardiomypathy patients,56 septic patients,and 31 controls were enrolled.IL-7 level was lower in septic cardiomypathy patients compared with in septic patients and controls[75.71(42.28,135.59)pg/mL vs.118.47(60.18,171.73)pg/mL vs.168.42(105.41,232.30)pg/mL,P<0.05].Soluble CD127 level was higher in septic cardiomypathy patients and septic patients compared with in controls[96.70(56.76,147.04)pg/mL vs.69.75(43.19,111.28)pg/mL vs.29.13(19.33,42.11)pg/mL,P<0.001].There was no significant difference of CD127+CD8+percentage among three groups(P=0.477).Th9 percentage and Foxo1 mRNA expression was lower in septic cardiomypathy patients compared with in septic patients and controls(P<0.001).Tc9 percentage,PU.1 mRNA expression and IL-9 level was lower

关 键 词：脓毒性心肌病 脓毒症 白细胞介素 辅助性T细胞 

分 类 号：R542.2[医药卫生—心血管疾病]