Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
Oxid Med Cell Longev. 2021 Oct 8;2021:6256399. doi: 10.1155/2021/6256399. eCollection 2021.
The main objective of this study was to investigate the diurnal differences in Period 2 (PER2) expression in myocardial ischemia-reperfusion (I/R) injury. We investigated diurnal variations in oxidative stress and energy metabolism after myocardial I/R in vitro and in vivo. In addition, we also analyzed the effects of HO treatment and serum shock in H9c2 cells transfected with silencing RNA against Per2 (siRNA-Per2) in vitro. We used C57BL/6 male mice to construct a model of I/R injury at zeitgeber time (ZT) 2 and ZT14 by synchronizing the circadian rhythms. Our in vivo analysis demonstrated that there were diurnal differences in the severity of injury caused by myocardial infarctions, with more injury occurring in the daytime. PER2 was significantly reduced in heart tissue in the daytime and was higher at night. Our results also showed that more severe injury of mitochondrial function in daytime produced more reactive oxygen species (ROS) and less ATP, which increased myocardial injury. In vitro, our findings presented a similar trend showing that apoptosis of H9c2 cells was increased when PER2 expression was lower. Meanwhile, downregulation of PER2 disrupted the oxidative balance by increasing ROS and mitochondrial injury. The result was a reduction in ATP and failure to provide sufficient energy protection for cardiomyocytes.
本研究的主要目的是探讨心肌缺血再灌注（I/R）损伤中 PER2 表达的昼夜差异。我们研究了体外和体内心肌 I/R 后氧化应激和能量代谢的昼夜变化。此外，我们还分析了 HO 处理和沉默 RNA 转染的 H9c2 细胞（siRNA-Per2）血清休克对 PER2 的影响。我们使用 C57BL/6 雄性小鼠在 Zeitgeber 时间（ZT）2 和 ZT14 构建 I/R 损伤模型，使昼夜节律同步。我们的体内分析表明，心肌梗死引起的损伤严重程度存在昼夜差异，白天损伤更严重。PER2 在白天的心脏组织中显著减少，夜间升高。我们的结果还表明，白天线粒体功能更严重的损伤会产生更多的活性氧（ROS）和更少的 ATP，从而增加心肌损伤。在体外，我们的发现呈现出相似的趋势，即当 PER2 表达较低时，H9c2 细胞的凋亡增加。同时，PER2 的下调通过增加 ROS 和线粒体损伤破坏了氧化平衡，导致 ATP 减少，无法为心肌细胞提供足够的能量保护。
