TCDD激活芳香烃受体减轻小鼠肾脏缺血再灌注损伤

发布时间：2018-01-24 21:08

本文关键词： 芳香烃受体 -四氯联苯对二恶英缺血再灌注损伤调节性T细胞　出处：《华中科技大学学报(医学版)》2013年03期 　论文类型：期刊论文

【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P0.05)。TCDD治疗组肾脏病理变化明显减轻,评分优于PBS对照组(P0.05)。体外实验中TCDD的干预明显提升了Treg细胞的比例(P0.05),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(P0.05)。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。
[Abstract]:Objective to study the relationship between 2-tetrachlorodibenzo-p-dioxin and dioxin. TCDD) activates arylhydrocarbon receptor. AHR) in ischemia-reperfusion injury of kidney of mice. Methods the model of renal ischemia-reperfusion injury in C57BL / 6 mice was established. TCDD treatment group (intraperitoneal injection of TCDD 0.5 渭 g / mouse 24 hours before operation) and PBS control group (intraperitoneal injection of PBS 200 渭 L / rat 24 hours before operation) were used. The survival time of each treatment group was observed, the pathological changes and scores were evaluated, and the peripheral blood creatinine was detected. Concentration of urea nitrogen. In vitro study on the differentiation of naive T cells into regulatory T cells (Treg cells) by TCDD. Flow cytometry was used to detect the spleen of IRI model mice. Results compared with the control group, the survival time of mice in the PBS treated group was significantly longer than that in the control group. Renal function (serum creatinine and urea nitrogen) was significantly improved (all P0.05A. TCDD treatment group kidney pathological changes were significantly reduced. The score was better than that of PBS control group (P 0.05). In vitro TCDD intervention significantly increased the proportion of Treg cells (P 0.05). In IRI model, TCDD activated AHR also significantly increased the proportion of Treg cells in spleen and peripheral blood (P0.05). Conclusion TCDD activated AHR can significantly improve renal function of renal ischemia reperfusion injury model in mice. The mechanism may be related to the expansion of Treg cell subsets selectively induced by TCDD.
【作者单位】：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;重庆医科大学附属永川医院肝胆外科;华中科技大学同济医学院附属同济医院胸心外科;
【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)
【分类号】：R363
【正文快照】： 缺血再灌注损伤(ischemia-reperfusion injury,IRI)是器官移植中影响移植物存活的重要因素,可导致移植物短期和长期功能损害,包括易于发生移植物原发性无功能、急性排斥反应、慢性移植物失功等,目前尚无特殊有效的治疗手段。以往关于IRI的研究主要集中在非免疫因素上,但是近

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