Institute of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Paediatric Orthopaedics Royal Children's Hospital, Glasgow, Scotland, UK.
Biomed Res Int. 2020 Nov 25;2020:8979270. doi: 10.1155/2020/8979270. eCollection 2020.
Dexmedetomidine (Dex) was reported to reduce oxidative stress and protect against myocardial Ischemia/Reperfusion (I/R) injury. However, the molecular mechanism involved in its antioxidant property is not fully elucidated. The present study was aimed at investigating whether the Trx1/Akt pathway participated in the cardioprotective effect of Dex. In the present study, I/R-induced myocardial injury in isolated rat hearts and OGD/R-induced injury in H9c2 cardiomyocytes were established. Our findings suggested that Dex ameliorated myocardial I/R injury by improving cardiac function, reducing myocardial apoptosis and oxidative stress, which was manifested by increased GSH and SOD contents, decreased ROS level, and MDA generation in both the isolated rat hearts and OGD/R-treated H9C2 cells. More importantly, it was found that the level of Trx1 was preserved, and Akt phosphorylation was significantly upregulated by Dex treatment. However, these effects of Dex were abolished by PX-12 (a specific Trx1 inhibitor) administration. Taken together, this study suggests that Dex plays a protective role in myocardial I/R injury, improves cardiac function, and relieves oxidative stress and cell apoptosis. Furthermore, our results present a novel signaling mechanism that the cardioprotective effect of Dex is at least partly achieved through the Trx1-dependent Akt pathway.
右美托咪定（Dex）被报道可减轻氧化应激并保护心肌免受缺血/再灌注（I / R）损伤。然而，其抗氧化特性涉及的分子机制尚未完全阐明。本研究旨在探讨 Trx1 / Akt 途径是否参与 Dex 的心脏保护作用。在本研究中，建立了分离的大鼠心脏 I / R 诱导的心肌损伤和 H9c2 心肌细胞 OGD / R 诱导的损伤模型。我们的研究结果表明，Dex 通过改善心脏功能，减少心肌细胞凋亡和氧化应激来减轻心肌 I / R 损伤，这表现在分离的大鼠心脏和 OGD / R 处理的 H9C2 细胞中，GSH 和 SOD 含量增加，ROS 水平降低，MDA 生成减少。更重要的是，发现 Dex 处理可保存 Trx1 的水平，并显著上调 Akt 的磷酸化。然而，Dex 的这些作用被 PX-12（一种特异性 Trx1 抑制剂）的给药所消除。总之，本研究表明 Dex 在心肌 I / R 损伤中发挥保护作用，改善心脏功能，并减轻氧化应激和细胞凋亡。此外，我们的结果提出了一种新的信号机制，即 Dex 的心脏保护作用至少部分是通过 Trx1 依赖性 Akt 途径实现的。
