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27 April 2019 : Animal Research  

Effects of Sevoflurane Pretreatment on Myocardial Ischemia-Reperfusion Injury Through the Akt/Hypoxia-Inducible Factor 1-alpha (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway

Jingwei Dong1ACDF, Mingjun Xu1BEF, Wenyu Zhang1ACE, Xiangming Che1ABEG*

DOI: 10.12659/MSM.914265

Med Sci Monit 2019; 25:3100-3107

Abstract

BACKGROUND: The aim of this study was to investigate the effects of sevoflurane (SEV) on myocardial ischemia/reperfusion (I/R) injury in rats and its mechanism.

MATERIAL AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into 3 groups: Sham group (n=20), I/R group (n=20) and I/R+SEV group (n=20). The I/R model was established by ligating and recanalizing the left anterior descending coronary artery (LAD). Triphenyl tetrazolium chloride (TTC) test and echocardiography (ECG) were used for analysis. Hematoxylin and eosin (H&E) staining was applied to detect the morphological changes. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect the apoptosis levels. The expression level of superoxide dismutase 2 (SOD2) was measured. Finally, the effect of SEV on the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway was detected via western blotting.

RESULTS: SEV could significantly improve I/R-induced cardiac insufficiency, inhibit cardiac infarction, and as well as reduce the infarction area from 53.21±2.11% to 32.33±3.49% (P<0.05). Compared with rats in I/R group, the cardiac myofilament was better in alignment, degradation and necrosis were milder, and cell edema was notably reduced in the I/R+SEV group. Thus, SEV could significantly reverse the decreased expression of SOD2 caused by I/R and reduce oxidative stress in the heart (P<0.05). According to the western blotting results, SEV was capable of obviously activating the expressions of phosphorylated-Akt (p-Akt), HIF-1α, and VEGF.

CONCLUSIONS: SEV can significantly improve myocardial injury caused by I/R in rats, and its mechanism might be related to the activation of the Akt/HIF-1α/VEGF signaling pathway.

Keywords: Hypoxia-Inducible Factor 1, alpha Subunit, Proto-Oncogene Proteins c-akt, Receptors, Vascular Endothelial Growth Factor, Reperfusion Injury, Apoptosis, Male, Myocardial Ischemia, Myocardial Reperfusion, Myocardial Reperfusion Injury, Random Allocation, Rats, Rats, Sprague-Dawley, sevoflurane, Signal Transduction, Vascular Endothelial Growth Factor A

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750