Ischemic heart disease (IHD) is a cardiovascular disease with high fatality rate, and its pathogenesis is closely related to oxidative stress. Reactive oxygen species (ROS) in oxidative stress can lead to myocardial ischemia (MI) injury in many ways. Therefore, the application of antioxidants may be an effective way to prevent IHD. In recent years, glutathione peroxidase 4 (GPx4) has received increasing attention due to its antioxidant effect. In a previous study, we used the new chimeric tRNA^UTuT6 to express highly active recombinant human GPx4 (rhGPx4) in amber-less Escherichia coli. In this study, we established an isoproterenol- (ISO-) induced MI injury model in rats and an in vitro model to research the protective effect and mechanism of rhGPx4 on MI injury. The results showed that rhGPx4 could reduce the area of myocardial infarction and ameliorate the pathological injury of heart tissue, significantly reduce ISO-induced abnormalities on electrocardiogram (ECG) and cardiac serum biomarkers, protect mitochondrial function, and attenuate cardiac oxidative stress injury. In an in vitro model, the results also confirmed that rhGPx4 could inhibit ISO-induced oxidative stress injury and cardiomyocyte apoptosis. The mechanism of action of rhGPx4 involves not only the inhibition of lipid peroxidation by eliminating ROS but also keeping a normal level of endogenous antioxidant enzymes by eliminating ROS, thereby preventing oxidative stress injury in cardiomyocytes. Additionally, rhGPx4 could inhibit cardiomyocyte apoptosis through a mitochondria-dependent pathway. In short, rhGPx4, a recombinant antioxidant enzyme, can play an important role in the prevention of IHD and may have great potential for application.

中文翻译：

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重组人谷胱甘肽过氧化物酶4对异丙肾上腺素所致心肌缺血损伤的保护作用及机制

缺血性心脏病（IHD）是一种致死率较高的心血管疾病，其发病机制与氧化应激密切相关。氧化应激中的活性氧 (ROS) 可通过多种方式导致心肌缺血 (MI) 损伤。因此，应用抗氧化剂可能是预防 IHD 的有效方法。近年来，谷胱甘肽过氧化物酶4（GPx4）因其抗氧化作用而受到越来越多的关注。在之前的一项研究中，我们使用新的嵌合 tRNA ^{UTuT6在无琥珀}大肠杆菌中表达高活性重组人 GPx4 (rhGPx4). 本研究建立异丙肾上腺素（ISO-）诱导大鼠心肌梗死损伤模型和体外模型，研究rhGPx4对心肌梗死损伤的保护作用及机制。结果表明，rhGPx4可以减少心肌梗死面积，改善心脏组织病理损伤，显着降低ISO引起的心电图（ECG）和心脏血清生物标志物异常，保护线粒体功能，减轻心脏氧化应激损伤。在体外模型中，结果还证实rhGPx4可以抑制ISO诱导的氧化应激损伤和心肌细胞凋亡。rhGPx4的作用机制不仅包括通过消除ROS来抑制脂质过氧化，还包括通过消除ROS来保持内源性抗氧化酶的正常水平，从而防止心肌细胞的氧化应激损伤。此外，rhGPx4 可以通过线粒体依赖性途径抑制心肌细胞凋亡。总之，重组抗氧化酶rhGPx4在IHD的预防中可以发挥重要作用，可能具有很大的应用潜力。