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

Hyperglycemia promotes T cell activation and aggravates myocardial dysfunction in diabetic mice

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。

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 lwk after STZ injection. Heart samples were stained with H＆E, and exainined 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 ＋ Thl cells may play an important role in pathogenesis of diabetic cardiomyopathy, and TNF-α may also contribute to this process.