Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway

• Published in: Clinical and experimental pharmacology & physiology Vol. 44; no. 9; pp. 946 - 953
• Main Authors: Sun, Yanjun, Jiang, Chuan, Jiang, Jun, Qiu, Lisheng
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.09.2017
• Subjects: 1-Phosphatidylinositol 3-kinase; Activated carbon; AKT protein; AMP; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Biomarkers - metabolism; Carbonyl compounds; Carbonyls; Catalase; Cytokines; dexmedetomidine; Dexmedetomidine - pharmacology; eNOS; Enzymes; Glutathione; Glutathione peroxidase; Heart; Heart diseases; Heart function; Hemodynamics; Inflammation; Inhibitors; Injuries; Interleukin 1; Interleukin 6; Ischemia; Kinases; Lethality; Mice; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium; Myocardium - metabolism; Myocardium - pathology; myocardium ischaemic/reperfusion injury; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Oxidative stress; Parameters; Peroxidase; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; PI3K/Akt; Protein kinase; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Reperfusion; Rodents; Signal transduction; Signal Transduction - drug effects; Superoxide dismutase; Surgery; Tumor necrosis factor-TNF; Tumors; AMPK; myocardium ischaemic/reperfusion injury; dexmedetomidine; eNOS; PI3K/Akt
• ISSN: 0305-1870; 1440-1681; 1440-1681
• DOI: 10.1111/1440-1681.12791

Summary Acute myocardial ischaemia/reperfusion (MIR) injury leads to severe arrhythmias and has a high rate of lethality. In the present study, we aim to determine the effect of dexmedetomidine (Dex) on heart injury parameters following MIR surgery. We examined the effects of Dex on heart function parameters and infarct size following MIR surgery. Proinflammatory cytokines, oxidative products and anti‐oxidative enzymes in the myocardium were measured to evaluate the anti‐inflammatory and anti‐oxidative effects of Dex. The role of the adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK)/phosphatidylino‐sitol 3‐kinase (PI3k)/Akt/endothelial nitric oxide synthase (eNOS) pathway was investigated using their inhibitors. The alteration of haemodynamic parameters, histopathological results, and infarct size caused by MIR was attenuated by Dex. The interleukine‐1 beta (IL‐1β), IL‐6, tumour necrosis factor‐a (TNF‐α) and myeloperoxidase (MPO) were all significantly decreased. Anti‐oxidative enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were restored by Dex. Oxidative products8‐OHdG, MDA and protein carbonyl were all decreased by Dex (P<.05). Dex activated AMPK expression, eNOS and Akt phosphorylation. The influence of Dex on cardiac function was reversed by the inhibitors of the eNOS, AMPK and PI3K/Akt pathways. These results indicate that Dex protected the cardiac functional, histological changes, inflammation and oxidative stress induced by MIR. Our results present a novel signalling mechanism that Dex protects MIR injury by activating an AMPK/PI3K/Akt/eNOS pathway.