microRNA‑22 attenuates myocardial ischemia‑reperfusion injury via an anti‑inflammatory mechanism in rats

Yang,Jian; Fan,Zhixing; Yang,Jun; Ding,Jiawang; Yang,Chaojun; Chen,Lihua

doi:10.3892/etm.2016.3777

microRNA‑22 attenuates myocardial ischemia‑reperfusion injury via an anti‑inflammatory mechanism in rats

Authors:
- Jian Yang
- Zhixing Fan
- Jun Yang
- Jiawang Ding
- Chaojun Yang
- Lihua Chen
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Affiliations: Department of Cardiology, Institute of Cardiovascular Diseases, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei 443000, P.R. China, Department of Optometry and Ophthalmology, Yichang Central People's Hospital, China Three Gorges University, Yichang, Hubei 443000, P.R. China
Published online on: October 4, 2016 https://doi.org/10.3892/etm.2016.3777
Pages: 3249-3255
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have reported that microRNA-22 (miR-22) may be implicated in ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published data also demonstrated that miR‑22 may protect against myocardial I/R injury via anti‑apoptosis in rats by targeting cAMP response element‑binding protein binding protein (CBP). However, the specific function of miR‑22 in myocardial I/R injury is far from fully elucidated. The present study was designed to investigate another cardioprotective signaling mechanism of miR‑22 in myocardial I/R injury. A total of 40 adult male Sprague‑Dawley rats were randomly divided into four equal groups (n=10): Sham, myocardial I/R, myocardial I/R with adenovirus expressing scramble miRNA (Ad‑Scramble) and myocardial I/R with adenovirus expressing miR‑22 (Ad‑miR‑22) groups. Besides the Sham operation group, the remaining three groups were artificially afflicted with coronary occlusion for 30 min and subsequently reperfused for 4 h. A light microscope was used to observe structural changes in the myocardium; reverse transcription polymerase chain reaction was used to measure the miR‑22 mRNA expression level; the myocardial infarct size was analyzed by the Evans Blue/triphenyltetrazolium chloride double‑staining; and p38 mitogen‑activated protein kinase (MAPK), CBP, c‑Jun‑activator protein (AP)‑1 and phospho (p)‑c‑Jun‑AP‑1 expression protein levels were detected by a western blot. Furthermore, ELISA was used to measure the levels of TNF‑α and IL‑6 in the myocardium. The results demonstrated that adenovirus‑mediated miR‑22 overexpression markedly reduced p38 MAPK, CBP, c‑Jun‑AP‑1, p‑c‑Jun‑AP‑1 expression levels concomitant with an improvement in myocardial injury, including smaller infarct size, reduced release of creatine kinase, lactate dehydrogenase and proinflammation mediators (tumor necrosis factor‑α and interleukin‑6). These findings suggest that miR‑22 has a protective effect on myocardial I/R injury. This protection mechanism, at least in part, is due to its anti‑inflammatory function via the suppression of the p38 MAPK/CBP/c‑Jun‑AP‑1 signaling pathway.

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