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

Dexmedetomidine postconditioning attenuates myocardial ischemia/reperfusion injury by activating the Nrf2/Sirt3/SOD2 signaling pathway in the rats.

机构信息

Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

出版信息

Redox Rep. 2023 Dec;28(1):2158526. doi: 10.1080/13510002.2022.2158526.

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 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.

目的

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 大鼠随机分为五组，分别接受不同的处理：假手术、缺血/再灌注（I/R）、Dex、Brusatol、Dex+Brusatol。通过建立大鼠心肌 IRI 模型，通过评估血清 CK-MB 和 cTnI 水平、心肌 HE 和 Tunel 染色以及梗死面积来评价 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 后处理显著减轻了心肌 IRI，降低了细胞内 ROS 和心肌组织 MDA 水平，增加了 SOD 和 GSH-PX 活性。Dex 后处理显著上调了心肌 Bcl-2 的表达，下调了 Bax 和 cleaved caspase-3 的表达，降低了心肌细胞凋亡率。此外，Dex 后处理促进了 Nrf2 的核转位，增加了心肌 Sirt3 和 SOD2 的表达，降低了 Ac-SOD2 的表达。然而，Brusatol 逆转了 Dex 后处理的心脏保护作用，显著降低了 Dex 诱导的 Nrf2 核转位，减少了心肌 Sirt3 和 SOD2 的表达。