Department of Anesthesiology, the Affiliated Changzhou No 2 People's Hospital of Nanjing Medical University, Changzhou 213100, Jiangsu, China.
Department of Anesthesiology, the Affiliated Changzhou No 2 People's Hospital of Nanjing Medical University, Changzhou 213100, Jiangsu, China.
Biomed Pharmacother. 2023 Sep;165:115185. doi: 10.1016/j.biopha.2023.115185. Epub 2023 Jul 22.
Myocardial ischemiareperfusion injury (MIRI) is defined as the additional damage that occurs during the process of restoring blood flow to the heart tissue after ischemia-induced damage. Ozone is a powerful oxidizer, but low concentrations of ozone can protect various organs from oxidative stress. Some studies have demonstrated a link between ozone and myocardioprotection, but the mechanism remains unclear. To establish an in vivo animal model of ischemiareperfusion injury (I/R), this study utilized C57 mice, while an in vitro model of hypoxia-reoxygenation (H/R) injury was developed using H9c2 cardiomyocytes to simulate ischemiareperfusion injury. Ozone pretreatment was used in in vitro and in vivo experiments. Through this research, we found that ozone therapy can reduce myocardial injury, and further studies found that ozone regulates the expression levels of these ferroptosis-related proteins and transcription factors in the H/R model, which were screened by bioinformatics. In particular, nuclear translocation of Nrf2 was enhanced by pretreatment with ozone, inhibited ferroptosis and ameliorated oxidative stress by initiating the expression of Slc7a11 and Gpx4. Significantly, Nrf2 gene silencing reverses the protective effects of ozone in the H/R model. In summary, our results suggest that ozone protects the myocardium from I/R damage through the Nrf2/Slc7a11/Gpx4 signaling pathway, highlighting the potential of ozone as a new coronary artery disease therapy.
心肌缺血再灌注损伤（MIRI）是指在缺血引起的损伤后恢复心脏组织血流时发生的额外损伤。臭氧是一种强大的氧化剂，但低浓度的臭氧可以保护各种器官免受氧化应激。一些研究表明臭氧与心肌保护之间存在联系，但机制尚不清楚。为了建立缺血再灌注损伤（I / R）的体内动物模型，本研究使用 C57 小鼠，而使用 H9c2 心肌细胞建立缺氧再复氧（H / R）损伤的体外模型模拟缺血再灌注损伤。在体外和体内实验中使用臭氧预处理。通过这项研究，我们发现臭氧治疗可以减轻心肌损伤，进一步的研究发现臭氧调节 H / R 模型中这些铁死亡相关蛋白和转录因子的表达水平，这些蛋白和转录因子是通过生物信息学筛选出来的。特别是，臭氧预处理增强了 Nrf2 的核易位，通过启动 Slc7a11 和 Gpx4 的表达抑制铁死亡和改善氧化应激。重要的是，Nrf2 基因沉默逆转了臭氧在 H / R 模型中的保护作用。总之，我们的结果表明，臭氧通过 Nrf2 / Slc7a11 / Gpx4 信号通路保护心肌免受 I / R 损伤，突出了臭氧作为一种新的冠心病治疗方法的潜力。
