TCDD激活芳香烃受体减轻小鼠肾脏缺血再灌注损伤  

TCDD Protects the Mouse Kidneys against Ischemia-reperfusion Injury by Activating the Aryl Hydrocarbon Receptor

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,器官移植教育部/卫生部重点实验室,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,武汉430030

出　　处：《华中科技大学学报（医学版）》2013年第3期254-257,272,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家重点基础研究发展计划(973计划)资助项目(No.2009CB522407);国家自然科学基金资助项目(No.30972794)

摘　　要：目的论证2,3,7,8-四氯联苯对二恶英(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)激活芳香烃受体(arylhydrocarbon receptor,AHR)在小鼠肾脏缺血再灌注损伤(ischemia-reperfusion injury,IRI)中的保护作用并探讨其机制。方法建立C57BL/6小鼠肾脏缺血再灌注损伤模型,设TCDD治疗组(术前24h腹腔注射TCDD 0.5μg/只)及PBS对照组(术前24h腹腔注射PBS 200μL/只),另设假手术组及正常组。观察各治疗组模型的生存时间,评估其病理变化并评分,检测外周血肌酐、尿素氮浓度。体外实验观察TCDD对初始型T细胞(naive T细胞)定向分化为调节性T细胞(Treg细胞)的影响。流式细胞技术检测IRI模型小鼠脾脏、外周血中Treg细胞的比例。结果与PBS对照组相比,TCDD治疗组小鼠生存时间明显延长,肾功能(血肌酐和尿素氮)明显改善(均P<0.05)。TCDD治疗组肾脏病理变化明显减轻,评分优于PBS对照组(P<0.05)。体外实验中TCDD的干预明显提升了Treg细胞的比例(P<0.05),而在IRI模型中TCDD激活AHR也显著提升了脾脏以及外周血中Treg细胞比例(P<0.05)。结论 TCDD激活AHR明显改善小鼠肾脏缺血再灌注损伤模型的肾功能,机制可能与TCDD选择性诱导Treg细胞亚群的扩增有关。Objective To investigate the protective effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin（TCDD）on ischemiareperfusion injury（IRI）of the kidneys in mice and the possible mechanism.Methods Kidney IRI models were established in C57BL/6（H-2b）mice.Animals were divided into TCDD-treated group（0.5μg TCDD intraperitoneally given to a mouse 24h before operation）,PBS control group（200μL PBS intraperitoneally administered to a mouse 24hbefore operation）,sham group and normal group.The life time of the animals was recorded,and the kidney function[blood urea nitrogen（BUN）and serum creatinine（Scr）]measured.Morphologic changes of the IRI kidney were evaluated by light microscopy.The effect of TCDD on the differentiation of naive T cells into regulatory T cells（Treg cells）was observed in vitro.The phenotype of T cells in the peripheral blood or spleens of IRI models was measured by flow cytometry.Results The life time was significantly prolonged and the kidney function improved in the TCDD-treated group as compared with those in the PBS control group（P〈0.05）.The pathological changes of the kidney in TCDD-treated group were significantly alleviated when compared with those in PBS control group.TCDD selectively expanded the subgroup of CD4＋CD25＋Foxp3＋regulatory T cells in vitro（P〈0.05）,as well as Treg cells in the peripheral blood and spleens of IRI models in vivo（P〈0.05）.Conclusion Activation of the arly hydrocarbon receptor（AHR）by TCDD could obviously improve the kidney function of IRI models,which may be associated with the expansion of the Treg cell subgroup.

关 键 词：芳香烃受体 2 3 7 8-四氯联苯对二恶英 缺血再灌注损伤 调节性T细胞 

分 类 号：R699.2[医药卫生—泌尿科学]