ABSTRACT

Objectives

To observe the protective effects of dexmedetomidine (Dex) postconditioning on myocardial ischemia/reperfusion injury (IRI) and to explore its potential molecular mechanisms.

Methods

One-hundred forty-seven male Sprague-Dawley rats were randomly divided into five groups receiving the different treatments: Sham, ischemia/reperfusion (I/R), Dex, Brusatol, Dex + Brusatol. By the in vivo rat model of myocardial IRI, cardioprotective effects of Dex postconditioning were evaluated by assessing serum CK-MB and cTnI levels, myocardial HE and Tunel staining and infarct size. Furthermore, the oxidative stress-related markers including intracellular ROS level, myocardial tissue MDA level, SOD and GSH-PX activities were determined.

Results

Dex postconditioning significantly alleviated myocardial IRI, decreased intracellular ROS and myocardial tissue MDA level, increased SOD and GSH-PX activities. Dex postconditioning significantly up-regulated myocardial expression of Bcl-2, down-regulated Bax and cleaved caspase-3 and decreased cardiomyocyte apoptosis rate. furthermores, Dex postconditioning promoted Nrf2 nuclear translocation, increased myocardial expression of Sirt3 and SOD2 and decreased Ac-SOD2. However, brusatol reversed cardioprotective benefits of Dex postconditioning, significantly decreased Dex-induced Nrf2 nuclear translocation and reduced myocardial expression of Sirt3 and SOD2.

Conclusions

Dex postconditioning can alleviate myocardial IRI by suppressing oxidative stress and apoptosis, and these beneficial effects are at least partly mediated by activating the Nrf2/Sirt3/SOD2 signaling pathway.

中文翻译：

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右美托咪定后处理通过激活 Nrf2/Sirt3/SOD2 信号通路减轻大鼠心肌缺血/再灌注损伤

摘要

目标

观察右美托咪定（Dex）后处理对心肌缺血/再灌注损伤（IRI）的保护作用，并探讨其潜在的分子机制。

方法

将 147 只雄性 Sprague-Dawley 大鼠随机分为接受不同治疗的五组：假手术、局部缺血/再灌注 (I/R)、Dex、Brusatol、Dex + Brusatol。通过心肌 IRI的体内大鼠模型，通过评估血清 CK-MB 和 cTnI 水平、心肌 HE 和 Tunel 染色以及梗塞面积来评估 Dex 后处理的心脏保护作用。此外，还测定了氧化应激相关标志物，包括细胞内 ROS 水平、心肌组织 MDA 水平、SOD 和 GSH-PX 活性。

结果

Dex后处理显着减轻心肌IRI，降低细胞内ROS和心肌组织MDA水平，增加SOD和GSH-PX活性。Dex后处理显着上调心肌Bcl-2表达，下调Bax和cleaved caspase-3，降低心肌细胞凋亡率。此外，Dex后处理促进Nrf2核转位，增加心肌Sirt3和SOD2表达，降低Ac-SOD2。然而，brusatol 逆转了 Dex 后处理的心脏保护作用，显着降低了 Dex 诱导的 Nrf2 核转位并降低了 Sirt3 和 SOD2 的心肌表达。

结论

Dex 后处理可以通过抑制氧化应激和细胞凋亡来减轻心肌 IRI，这些有益作用至少部分是通过激活 Nrf2/Sirt3/SOD2 信号通路介导的。