聚乙二醇-过氧化氢酶在小鼠心肌肥厚和损伤中的保护作用

Polyethylene glycol-Catalase attenuates isoproterenol induced mouse heart hypertrophy and injury

目的观察聚乙二醇-过氧化氢酶在异丙肾上腺素所致小鼠心肌肥厚和损伤中的保护作用。方法以异丙肾上腺素建立C57BL/6小鼠心肌肥厚和心肌损伤的模型,通过二氢乙啶染色、蛋白质印迹法、实时定量逆转录聚合酶链反应、Masson Trichrome染色等实验,检测聚乙二醇-过氧化氢酶在异丙肾上腺素所致小鼠心肌肥厚和损伤模型中对氧自由基生成、细胞凋亡、心肌纤维化、超氧化物歧化酶1(SOD-1)表达的影响。结果小鼠异丙肾上腺素皮下注射后,发生心肌肥厚和缺血损伤,心肌组织氧自由基生成明显升高,SOD-1的表达明显降低,心肌细胞凋亡增加,发生心肌纤维化,与对照组对比差异有统计学意义(均为P<0.01);与异丙肾上腺素处理组比较,聚乙二醇-过氧化氢酶(30 000 U.kg-1.d-1)预处理组心肌肥厚改善,氧自由基生成明显降低,SOD-1水平明显提高,细胞凋亡减少,心肌纤维化降低,差异有统计学意义(均为P<0.05)。结论抗氧化剂聚乙二醇-过氧化氢酶可以有效进入心肌组织,抑制氧自由基生成、减少心肌细胞凋亡和心肌纤维化,对异丙肾上腺素诱导的小鼠心肌肥厚和损伤具有保护作用。

Objective To investigate the protective effects of polyethylene glycol-Catalase on isoproterenol-induced heart hypertrophy and injury. Methods The heart hypertrophy and injury model was developed by 40 ng· kg^-1 ·d^-1 of isoproterenol sc in mice. The myocardial ROS production, SOD-1 expression, apoptotic cell rate and myocardial fibrosis were analyzed by DHE staining, Western blot, real- time RT-PCR and Masson Trichrome staining. Results The heart ROS production, cell apoptosis rate and myocardial fibrosis increased obviously in model group after isoproterenol treatment, meanwhile the SOD-1 expression was decreased significantly （P 〈 0. 01 vs. Sham group）. In mice injured by isoproterenol and treated with 30 000 U · kg^-1 ·d^-1 polyethylene glycol-Catalase, ROS production, cell apoptosis and myocardial fibrosis decreased, while SOD-1 expression were increased （ all P 〈 0. 05 vs. isoprotereno] treated group）. Conclusions The results showed that polyethylene glycol-Catalase could effectively be transported into mouse heart and attenuate heart hypertrophy and injury by inhibiting ROS production, cell apoptosis, and myocardial fibrosis in mouse.