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  • 张辉,周晓慧,林芳,等.高血糖促进T细胞激活加重糖尿病小鼠心肌功能障碍的作用[J].同济大学学报(医学版),2016,37(6):1-5, 17.    [点击复制]
  • ZHANG Hui,ZHOU Xiao-hui,LIN Fang,et al.Hyperglycemia promotes T cell activation and aggravates myocardial dysfunction in diabetic mice[J].同济大学学报(医学版),2016,37(6):1-5, 17.   [点击复制]
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高血糖促进T细胞激活加重糖尿病小鼠心肌功能障碍的作用
张辉,周晓慧,林芳,铁金军,范慧敏,刘中民
0
(同济大学附属东方医院心外科,上海 200120;同济大学附属东方医院,心力衰竭研究所,上海 200120;上海市心力衰竭研究中心,上海 200120)
摘要:
目的 研究CD4+T细胞在糖尿病性心肌病(diabetes cardiomyopathy, DCM)中的作用。方法 SPF级C57BL/6小鼠,雄性,4周龄,饲喂高脂饲料(high fat diet, HFD)6周,腹腔注射链脲菌素(streptozotocin, STZ),普通饲料喂养的C57BL/6小鼠作为对照,饲喂6周后腹腔注射柠檬酸缓冲液。注射1周后两组小鼠做心脏超声检测,后处死小鼠,心肌组织进行H-E染色,观察心肌病理改变情况,Q-PCR检测两组小鼠心肌组织中相关炎症因子的表达水平。流式细胞检测小鼠体内CD4+T细胞的表型。结果 与普通饮食喂养小鼠相比,2型糖尿病模型小鼠出现了明显的心功能损害和心肌病理学改变。糖尿病模型小鼠心肌组织中Th1细胞转录因子T-bet及炎症因子TNF-α和IFN-γmRNA均较对照组明显升高。糖尿病模型小鼠纵隔淋巴结中CD4+CD44+T细胞比例较对照组明显升高。结论 2型糖尿病模型小鼠出现了明显的心功能损害,纵隔淋巴结CD4+CD44+T细胞比例明显增加,心肌组织中Th1细胞转录因子T-bet升高,提示激活的CD4+Th1细胞可能在DCM中扮演着重要角色,TNF-α可能也参与了这一过程。
关键词:  糖尿病性心肌病  CD4+T细胞  炎症反应  小鼠
DOI:10.16118/j.1008-0392.2016.06.001
投稿时间:2016-08-23
基金项目:国家自然科学基金(81470393、81370434、81400363、81670458);上海市领军人才基金(2012053);上海市卫计委(ZY3-LCPT-2-1003);浦东新区卫计委重点学科群建设(PWZxq2014-01);浦东新区科委(Pkj2013-z03)
Hyperglycemia promotes T cell activation and aggravates myocardial dysfunction in diabetic mice
ZHANG Hui,ZHOU Xiao-hui,LIN Fang,TIE Jin-jun,FAN Hui-min,LIU Zhong-min
(Dept.of Cardiac Surgery, East Hospital, Tongji University, Shanghai 200120, China;Research Institute of Heart Failure, East Hospital, Tongji University, Shanghai 200120, China;Shanghai Heart Failure Research Center, Shanghai 200120, China)
Abstract:
Objective To determine the role of CD4 + T cells in diabetic cardiomyopathy(DCM). Methods C57BL/6 mice(4wk old)were fed with High-fat diet(HFD)for 6wk, and then injected with streptozotocin, STZ intraperitoneally; and normal diet-fed C57BL/6 mice were injected with citric acid buffer as control. Echocardiographic assessment of heart function was performed and the hearts were harvested 1wk after STZ injection. Heart samples were stained with H&E, and examined under light microscopy. Inflammatory factors in hearts were evaluated by Q-PCR. T cells phenotypes were detected by Q-PCR and flow cytometry. Results Compared to control mice, type 2 diabetic mice showed significant heart dysfunction and myocardial pathological changes. mRNA levels of TNF-α and IFN-γ in HFD heart increased compared with ordinary diet mice. Percentages of CD4+CD44+T cells from mediastinal lymph node up-regulated compared to that from ordinary diet mice. Conclusion Results indicate that activation of CD4+ Th1 cells may play an important role in pathogenesis of diabetic cardiomyopathy, and TNF-α may also contribute to this process.
Key words:  diabetic cardiomyopathy(DCM)  CD4 + T cells  inflammation  mouse

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