Dexmedetomidine Postconditioning Attenuates Myocardial Ischemia/reperfusion Injury by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway in the Rats

Overview

Journal Redox Rep

Specialties Biochemistry
Biology
Endocrinology

Date 2023 Feb 4

PMID 36738240

Authors

Bin Hu

Tian Tian

Xin-Tao Li

Pei-Pei Hao

Wei-Chao Liu

Ying-Gui Chen

Tian-Yu Jiang

Pei-Shan Chen

Yi Cheng

Fu-Shan Xue

Affiliations

Soon will be listed here.

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 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.

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