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.

中文翻译：

---

右美托咪定可通过Trx1依赖的Akt途径减轻氧化应激和细胞凋亡，从而预防心肌缺血/再灌注损伤。

据报道，右美托咪定（Dex）可降低氧化应激并保护其免受心肌缺血/再灌注（I / R）损伤。但是，尚未完全阐明涉及其抗氧化性能的分子机理。本研究旨在调查Trx1 / Akt途径是否参与了Dex的心脏保护作用。在本研究中，建立了I / R诱导的离体大鼠心脏心肌损伤和OGD / R诱导的H9c2心肌细胞损伤。我们的发现表明，Dex通过改善心脏功能，减少心肌细胞凋亡和氧化应激来改善心肌I / R损伤，这表现为离体大鼠心脏和OGD / R的GSH和SOD含量增加，ROS水平降低和MDA产生-处理的H9C2细胞。更重要的是，发现通过Dex处理可以保持Trx1的水平，并且显着上调Akt的磷酸化。但是，PX-12（一种特定的Trx1抑制剂）给药消除了Dex的这些作用。两者合计，这项研究表明Dex在心肌I / R损伤中起保护作用，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传导机制，即Dex的心脏保护作用至少部分通过Trx1依赖性Akt途径实现。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传导机制，即Dex的心脏保护作用至少部分通过Trx1依赖性Akt途径实现。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传导机制，即Dex的心脏保护作用至少部分通过Trx1依赖性Akt途径实现。