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.

Background: Post-operative acute kidney injury (AKI) is one of the most common and serious complications after major surgery and is significantly associated with increased risks of morbidity and mortality. This meta-analysis was conducted to evaluate the effects of perioperative dexmedetomidine (Dex) administration on the occurrence of AKI and the outcomes of recovery after noncardiac surgery. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for studies comparing the effects of Dex vs. placebo on kidney function after non-cardiac surgery, and a pooled fixed-effect meta-analysis of the included studies was performed. The primary outcome was the occurence of post-operative AKI. The secondary outcomes included the occurence of intra-operative hypotension and bradycardia, intensive care unit (ICU) admission, duration of ICU stay, and hospital length of stay (LOS). Results: Six studies, including four randomized controlled trials (RCTs) and two observational studies, with a total of 2586 patients were selected. Compared with placebo, Dex administration could not reduce the odds of post-operative AKI (odds ratio [OR], 0.44; 95% confidence interval (CI), 0.18-1.06; P = 0.07; I 2 = 0.00%, P = 0.72) in RCTs, but it showed a significant renoprotective effect (OR, 0.67; 95% CI, 0.48-0.95; P = 0.02; I 2 = 0.00%, P = 0.36) in observational studies. Besides, Dex administration significantly increased the odds of intra-operative bradycardia and shortened the duration of ICU stay. However, there was no significant difference in the odds of intra-operative hypotension, ICU admission, and hospital LOS. Conclusions: This meta-analysis suggests that perioperative Dex administration does not reduce the risk of AKI after non-cardiac surgery. However, the quality of evidence for this result is low due to imprecision and inconsistent types of non-cardiac operations. Thus, large and high-quality RCTs are needed to verify the real effects of perioperative Dex administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery.