【摘要】 目的 探讨信号转导及转录激活因子5A(STAT5A)在血管紧张素Ⅱ（AngⅡ）诱导的心脏重构中的作用及其潜在机制。方法 12只雄性C57BL/6小鼠随机分为Saline组（n=6）与Ang组（n=6）,AngⅡ组采用AngⅡ[1.5 mg/（kg·d）](1次/日，皮下注射，持续4周)建立小鼠心脏重构模型，并验证模型构建成功。另取24只雄性C57BL/6小鼠随机分为Saline-oeNC、Saline-oeSTAT5A、AngⅡ-oeNC和AngⅡ-oeSTAT5A组，每组各6只，于AngⅡ处理开始前2周经尾静脉注射AAV9-STAT5A或空载体。评估各组小鼠心功能如左心室射血分数（LVEF）和缩短分数（LVFS），左心室内径如舒张末期左室内径（LVIDd）、收缩末期左室内径（LVIDs）及心肌纤维化；取各组左心室心肌组织行Western blot及免疫组化检测STAT5A蛋白表达。体外以原代心脏成纤维细胞敲低STAT5A后给予AngⅡ刺激，检测α-平滑肌肌动蛋白（α-SMA）评估肌成纤维细胞转化。结果 与Saline组相比，AngⅡ诱导模型中心肌STAT5A蛋白表达显著降低（P<0.01）。STAT5A过表达可显著改善AngⅡ诱导的心功能损伤（LVEF、LVFS升高），并抑制左心室扩张（LVIDd、LVIDs降低，P<0.01）；同时显著减轻心肌纤维化并抑制肌成纤维细胞转化（P<0.01）。相反，体外敲低STAT5A可进一步加重AngⅡ诱导的肌成纤维细胞转化（P<0.01）。结论 STAT5A在AngⅡ诱导的心脏重构中发挥重要的保护作用，其机制可能与抑制心肌纤维化和肌成纤维细胞转化有关，为心脏重构的治疗提供了新的靶点。更多还原

【Abstract】 Objective To discuss the effect and potential mechanism of signal transducer and activator of transcription5 A(STAT5 A) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac remodeling model.Methods Twelve male C57BL/6 mice were randomly divided into Saline group(n=6) and AngⅡ group(n=6).Ang Ⅱ group was administered AngⅡ [1.5 mg/(kg·d)] by subcutaneous inj ection once daily for 4 weeks to establish a mouse cardiac remodeling model,and the successful establishment of the model was verified.Another 24 male C57BL/6 mice were randomly divided into 4 groups:Saline-oeNC,Saline-oeSTAT5A,Ang Ⅱ-oeNC,and Ang Ⅱ-oeSTAT5A,with 6 mice in each group.AAV9-STAT5A or empty vector was injected via the tail vein2 weeks before the initiation of Ang Ⅱ treatment.The indicators of cardiac function were evaluated in each group,including left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS),left ventricular internal dimensions including left ventricular internal dimension at diastole(LVIDd) and left ventricular internal dimension at systole(LVIDs),as well as myocardial fibrosis.The left ventricular myocardial tissues were collected from each group for the detection of STAT5A protein expression by using Western blotting assay and immunohistochemistry.In vitro,primary cardiac fibroblasts were transfected to knock down STAT5A and then stimulated with Ang Ⅱ.The expression of α-smooth muscle actin(a-SMA) was detected to assess myofibroblast transformation.Results Compared with Saline group,the protein expression of myocardial STAT5A was significantly decreased in Ang Ⅱ group(P<0.01).The overexpression of STAT5A significantly ameliorated Ang Ⅱ-induced cardiac dysfunction(increased LVEF and LVFS) and inhibited left ventricular dilation(decreased LVIDd and LVIDs,P<0.01).Meanwhile,it significantly alleviated myocardial fibrosis and suppressed myofibroblast transformation(P<0.01).In contrast,knockdown of STAT5A in vitro further aggravated Ang Ⅱ-induced myofibroblast transformation(P<0.01).Conclusion STAT5A plays an important protective role in Ang Ⅱ-induced cardiac remodeling,and its mechanism may be related to the inhibition of myocardial fibrosis and myofibroblast transformation,providing a novel target for the treatment of cardiac remodeling.更多还原