激活芳香烃受体抑制同种异体小鼠心脏移植物急性排斥反应  

Activation of Aryl Hydrocarbon Receptor Suppresses Acute Rejection in Allogeneic Cardiac Transplantation

作　　者：蔡兰军[1] 余道武[2] 高义[1] 杨超[1] 周鸿敏[3] 陈忠华 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,湖北武汉430030 [2]重庆医科大学附属永川医院肝胆外科,重庆402160 [3]华中科技大学同济医学院附属同济医院胸心外科,湖北武汉430030

出　　处：《武汉大学学报（医学版）》2013年第3期321-324,338,共5页Medical Journal of Wuhan University

基　　金：国家重点基础研究发展计划(973)资助项目(编号:2009CB522407);国家自然科学基金资助项目(编号:30972794)

摘　　要：目的:验证在小鼠心脏移植中,2,3,7,8-四氯二苯二氧芑(TCDD)激活芳香烃受体(AHR)是否可以诱导调节性T细胞(Treg)扩增以及减轻急性排斥反应。方法:建立小鼠心脏移植模型,给予TCDD,观察对排斥反应及移植物生存期的影响。体外实验评估TCDD对Treg细胞比例的影响。检测受者体内Treg细胞比例及白细胞介素(白介素)-10表达水平。结果:TCDD激活AHR明显减轻心脏移植物内急性排斥反应,延长移植物存活时间[MST=(23.5±7.7)d]。体外实验中TCDD明显提升CD4+CD25+Foxp3+调节性T细胞比例[TCDD组(15.3±2.6)%;PBS组(4.7±2.4)%,P<0.01)],而受者体内脾脏和移植物内Treg细胞比例相比对照组也明显升高(P<0.05)。同时,TCDD明显提升了受者体内白介素-10的表达水平。结论:术前单次给予TCDD激活AHR可以明显抑制小鼠同种心脏移植物急性排斥反应,其机制可能与扩增Treg亚群有关。Objective： To verify whether activation of the aryl hydrocarbon receptor（AHR） with 2,3,7,8-tetrachlorodibenzo-p-dioxin（TCDD） could expand regulatory T cell subgroup and suppress acute cardiac allograft rejection.Methods： Mouse allogeneic cardiac transplantation from BALB/c（H-2d） to C57BL/6（H-2b） was performed with TCDD/PBS treatment to investigate the severity of acute rejection and the survival of allografts.In vitro,we performed lymphocyte proliferation assay to evaluate the selective expansion effect of TCDD on Treg cells.Phenotype of T cells or expression of IL-10 in recipients was measured by flowcytometry or enzyme linked immunosorbent assay.Results： Activation of the AHR with TCDD significantly suppressed the acute rejection and prolonged the survival of allografts（MST = 23.5 ± 7. 7 days）.TCDD expanded the subgroup of CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells in vitro（15.3% ± 2. 6% vs 4.7% ± 2.4% in PBS group,P〈 0.01）,as well as in spleens and allografts of recipients in vivo（P〈 0.05）.The expression of IL-10 was significantly elevated by the activation of the AHR.Conclusion： Activation of the AHR with single dose of TCDD significantly suppressed acute rejection of allografts,which was associated with the induction of Treg cells by TCDD.

关 键 词：芳香烃受体 2 3 7 8-四氯二苯二氧芑 心脏移植 急性排斥 调节性T细胞 

分 类 号：R392.4[医药卫生—免疫学]