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.