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. 2019 Apr 27:25:3100-3107.
doi: 10.12659/MSM.914265.

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 Dong  1 , Mingjun Xu  1 , Wenyu Zhang  1 , Xiangming Che  1
Affiliations

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 Dong et al. Med Sci Monit. .

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-1alpha)/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-1alpha, 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-1alpha/VEGF signaling pathway.

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Conflict of interest statement

Conflict of interest

None.

Figures

Figure 1
Figure 1
Process flow chart of rats in each group. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group.
Figure 2
Figure 2
Effect of SEV pretreatment on cardiac function in rats in each group. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group. * P<0.05 versus Sham group, and # P<0.05 versus I/R group.
Figure 3
Figure 3
Effect of SEV pretreatment on the heart infarction area of rats in each group. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group. * P<0.05 versus Sham group and # P<0.05 versus I/R group.
Figure 4
Figure 4
Effect of SEV pretreatment on the cardiac structure in each group of rats. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group.
Figure 5
Figure 5
Effect of SEV pretreatment on the apoptosis of myocardial cells in each group of rats. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group. * P<0.05 versus Sham group and # P<0.05 versus I/R group.
Figure 6
Figure 6
Effect of SEV pretreatment on the oxidative stress level in the myocardial tissue of rats in each group. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group. * P<0.05 versus Sham group and # P<0.05 versus I/R group.
Figure 7
Figure 7
Effect of SEV pretreatment on the Akt/HIF-1α/VEGF signaling pathway in the heart tissue of rats in each group. Sham – sham operation group; I/R – I/R group; I/R+SEV − I/R+SEV pretreatment group. * P<0.05 versus Sham group and # P<0.05 versus I/R group.
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