Departments of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Emergency, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Bioengineered. 2022 Jan;13(1):1377-1387. doi: 10.1080/21655979.2021.2017611.
Dexmedetomidine (DEX) has been reported to attenuate the ischemia and reperfusion (I/R) induced cardiomyocyte apoptosis. However, mechanisms underlying these protective effect remain to be fully elucidated. Cardiomyocyte apoptosis is associated with ischemic heart disease. Here we investigated the role of DEX in I/R -induced cardiomyocyte apoptosis. Mice and H9c2 cardiomyocyte cells were subjected to cardiomyocyte I/R injury and hypoxia/reoxygenation (H/R) injury, respectively. The roles and mechanisms of DEX on H9c2 cardiomyocyte cells and mice cardiomyocyte cells exposured to H/R or I/R injury were explored. The results showed that DEX attenuates H/R injury-induced H9c2 cell apoptosis and alleviated mitochondrial oxidative stress; it also reduced myocardial infarct size and protected the cardiac function following cardiomyocyte I/R injury. In addition, H/R and I/R injury increased p53 expression and forkhead box O3a (FOXO3a)/p53-upregulated modulator of apoptosis (PUMA) signaling in H9c2 cardiomyocyte cells and cardiomyocytes. Targeting p53 expression or FOXO3a/PUMA signaling inhibited cell apoptosis and protected against H/R injury in H9c2 cardiomyocyte cells and cardiomyocytes. Pretreatment with DEX reduced the H/R or I/R injury-induced activation of p53 expression and FOXO3a/PUMA signaling, and alleviated H/R or I/R injury-induced apoptosis and mitochondrial oxidative stress. Therefore, DEX could alleviate H/R- or I/R-induced cardiomyocytes injury by reducing cell apoptosis and blocking p53 expression and FOXO3a/PUMA signaling. Targeting p53 or/and FOXO3a/PUMA signaling could alleviate cardiomyocyte I/R injury.
右美托咪定（DEX）已被报道可减轻缺血再灌注（I/R）引起的心肌细胞凋亡。然而，其保护作用的机制仍有待充分阐明。心肌细胞凋亡与缺血性心脏病有关。在这里，我们研究了 DEX 在 I/R 诱导的心肌细胞凋亡中的作用。分别将小鼠和 H9c2 心肌细胞置于心肌 I/R 损伤和缺氧/复氧（H/R）损伤中。探讨了 DEX 对 H9c2 心肌细胞和暴露于 H/R 或 I/R 损伤的小鼠心肌细胞的作用及其机制。结果表明，DEX 减轻了 H/R 损伤诱导的 H9c2 细胞凋亡并减轻了线粒体氧化应激；它还减少了心肌梗死面积并保护了心肌细胞 I/R 损伤后的心脏功能。此外，H/R 和 I/R 损伤增加了 H9c2 心肌细胞和心肌细胞中的 p53 表达和叉头框 O3a（FOXO3a）/p53 上调凋亡调节剂（PUMA）信号。靶向 p53 表达或 FOXO3a/PUMA 信号抑制细胞凋亡并保护 H9c2 心肌细胞和心肌细胞免受 H/R 损伤。DEX 预处理可降低 H/R 或 I/R 损伤诱导的 p53 表达和 FOXO3a/PUMA 信号的激活，并减轻 H/R 或 I/R 损伤诱导的细胞凋亡和线粒体氧化应激。因此，DEX 通过减少细胞凋亡和阻断 p53 表达和 FOXO3a/PUMA 信号来减轻 H/R 或 I/R 诱导的心肌细胞损伤。靶向 p53 或/和 FOXO3a/PUMA 信号可减轻心肌 I/R 损伤。
