Eur Rev Med Pharmacol Sci 2019; 23 (4): 1730-1741

DOI: 10.26355/eurrev_201902_17135

Down-regulation of miR-320 exerts protective effects on myocardial I-R injury via facilitating Nrf2 expression

X.-A. Zhu, L.-F. Gao, Z.-G. Zhang, D.-K. Xiang

Department of Cardiovascular Surgery, Guizhou People’s Hospital, Guiyang, Guizhou, China. zhanqienei07@163.com


OBJECTIVE: Nuclear factor NF-E2 related factor 2 (Nrf2) plays crucial roles in the regulation of oxidative stress (OS) or myocardial ischemia-reperfusion (I-R) injury. During the process of I-R injury, the miR-320 is down-regulated. Bioinformatics analysis showed complementary binding sites between miR-320 and 3’-UTR of Nrf2 mRNA. Therefore, this study aimed to investigate the role of miR-320 in mediating Nrf2 expression and myocardial I-R injury.

MATERIALS AND METHODS: Rat I-R model was established. Fluorescent quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure the expression of miR-320, Nrf2, HO-1 in myocardial tissues. Contents of malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity, serum assay of creatine kinase (CK) and lactate dehydrogenase (LDH) activity were evaluated. I-R rat models were transfected with antagomir-320 followed by measuring those proteins. Cultured H9C2 cells were transfected with antagomir-320 to measure miR-320, Nrf2 and heme oxygenase 1 (HO-1) expression, cell apoptosis and reactive oxygen species (ROS) content.

RESULTS: Compared to the sham group, I-R rats had significantly lower miR-320 or HO-1 expression in the myocardium, plus higher levels of Nrf2, MDA, CK and LDH, and decreased SOD activity (p<0.05). Antagomir-320 transfection suppressed miR-320 expression, elevated Nrf2 and HO-1 expression, decreased levels of MDA, CK or LDH, and increased SOD activity. In H9C2 cells, antagomir-320 transfection also elevated Nrf2 and HO-1 expression and suppressed myocardial cell apoptosis or ROS production under I-R treatment.

CONCLUSIONS: Down-regulation of miR-320 exerts protective effects on myocardial I-R injury. The inhibition of mir-320 expression can enhance OS potency of the myocardium, alleviate I-R injury or reduce cell apoptosis by facilitating Nrf2 expression.

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To cite this article

X.-A. Zhu, L.-F. Gao, Z.-G. Zhang, D.-K. Xiang
Down-regulation of miR-320 exerts protective effects on myocardial I-R injury via facilitating Nrf2 expression

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 4
Pages: 1730-1741
DOI: 10.26355/eurrev_201902_17135