MiR-506 alleviates myocardial ischemia-reperfusion injury via targeting PI3K/AKT

M. Zhang, J.-Y. Wang, L. Li, G.-M. Li

Department of Anesthesiology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China. hayyzhm@njmu.edu.cn

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• Cardiology

OBJECTIVE: The aim of this study was to explore the effects of micro ribonucleic acid (miR)-506 and phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) pathway on myocardial ischemia-reperfusion injury (MIRI) in rats.

MATERIALS AND METHODS: A total of 90 healthy rats weighing 260-300 g were selected as research subjects, and divided into three groups, including: Control group (n=30), IR group (n=30), and miRNA treatment group (IR + miR-506 group, n=30). The model was successfully established via threading the coronary artery. The structural differences in myocardial tissues were observed via hematoxylin-eosin (HE) staining in each group. The mRNA expressions of miR-506 and PI3K in myocardial tissues were detected using fluorescence quantitative Polymerase Chain Reaction (qPCR). Meanwhile, AKT protein phosphorylation activity in myocardial tissues was detected as well. The apoptosis of myocardial tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. In addition, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardial tissues were compared in each group.

RESULTS: In Control group, no structural abnormalities were found in myocardial tissues, and no inflammatory cells were observed. In IR group, myocardial tissues were arranged disorderly, and inflammatory cell infiltration was found. In IR + miR-506 group, myocardial tissue lesions were milder than those in the IR group. qPCR results indicated that the mRNA expressions of miR-506 and PI3K in myocardial tissues were statistically different among groups (p<0.05), with the lowest in the IR group. The expression of miR-506 was evidently higher in IR + miR-506 group than that in the Control group (p<0.05). However, the mRNA expression of PI3K was significantly higher in the Control group than IR + miR-506 group (p<0.05). There was a significant positive correlation between the expressions of miR-506 and PI3K in each group (p<0.05). The phosphorylation activity of AKT protein in IR + miR-506 group was markedly higher than the other two groups (p<0.05). In addition, TUNEL staining demonstrated that the apoptosis rate in Control group, IR group and IR + miR-506 group was only 1.3%, 20.3%, and 9.8%, respectively. SOD activity was remarkably stronger in the Control group (62.7 U/mg pro) than the other two groups (p<0.05). In addition, MDA content was remarkably higher in IR group (0.747 nmol/mg pro) than that in the other two groups (p<0.05).

CONCLUSIONS: MiR-506 is associated with myocardial injury in rats, which can alleviate myocardial injury through the PI3K/AKT signaling pathway.

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