还原应激诱导心肌特异性高表达Hsp27小鼠发生心肌肥厚

Reductive stress induces myocardial hypertrophy in transgenic mice with cardiac-specific overexpression of heat shock protein 27

目的探讨热休克蛋白27(Hsp27)高表达引起小鼠心肌肥厚的作用机制。方法构建心肌中特异性高表达Hsp27的转基因(TG)小鼠和对照品系野生型(WT)小鼠。采用HE染色和异硫氰酸荧光素-麦胚凝集素(FITC-WGA)染色分别检测心脏体积和心肌面积,Western blot检测谷胱甘肽氧化物酶1(GPx1)蛋白表达,试剂盒测定活性氧(ROS)、丙二醛(MDA)以及还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)水平。注射GPx1抑制剂马拉松(MS)后,观察TG小鼠心功能的变化,计算心脏重/体重(HW/BW)和心脏重/胫骨长(HW/TL)比值。结果与WT小鼠相比,TG小鼠心脏体积和心肌面积增大,ROS和MDA水平降低(P<0.01),GSH含量和GSH/GSSG比值以及GPx1蛋白表达均增加(P<0.01)。注射MS后,TG小鼠心脏的射血分数和短轴缩短率增加,而HW/BW和HW/TL比值降低。结论 Hsp27高表达引起的还原应激可能在小鼠心肌肥大发生、发展过程中发挥着重要作用。

Objective To investigate the underlying mechanism of myocardial hypertrophy in mice overexpressed heat shock protein 27 （Hsp27）. Methods Transgenic （TG） mice with cardiacspecific overexpression of Hsp27 were constructed, and wild-type （WT） mice were taken as the controls. The size of heart and area of myocardium were determined by HE staining and FITC-WGA staining, respectively. The protein expression of glutathione peroxidase 1 （GPxl） was detected by Western blot, and the levels of reactive oxygen species （ROS）, malondialdehyde （MDA）, reduced glutathione（GSH） and oxidized glutathione（GSSO） were measured. After injection of GPxl inhibitor MS, the change of cardiac function was observed by echocardiography,and the ratios of heat weight to body weight（HW/BW） and heat weight to tibia length（HW/TL） were calculated. Results Compared with WT mice, the size of heart and area of myocardium were enlarged, the levels of ROS and MDA were decreased（P〈0. 01）, while GSH content, GSH/GSSG and GPxl expression were increased in TG mice（P〈0. 01）. Moreover, ejection fraction and fraction shortening of the heart were increased, while HW/BW and HW/TL were decreased in TG mice after injection of MS. Conclusion Reductive stress induced by overexpression of Hsp27 may play an important role in the development and progression of myocardial hypertrophy.