HOTAIR/miR-17-5p Axis is Involved in the Propofol-Mediated Cardioprotection Against Ischemia/Reperfusion Injury

Abstract

Junyang Chen,1 Xuefeng Li,1 Feng Zhao,2 Yubo Hu1 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of China; 2Department of Operating Room, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaCorrespondence: Yubo HuDepartment of Anesthesiology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, Jilin 130033, People’s Republic of ChinaEmail [email protected]: Propofol (PPF) ameliorates ischemia/reperfusion (I/R) injury in multiple organs by reducing apoptosis and release of pro-inflammatory cytokines. This study aims to explore the mechanism of PPF in attenuating myocardial ischemia-reperfusion injury (MIRI).Materials and Methods: Rat MIRI model was established, and PPF pre-treatment was performed 10 min before I/R. H9c2 cardiomyocytes treated with hypoxia/reoxygenation (H/R) were used to establish an in vitro model. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate HOTAIR and miR-17-5p expression levels. Flow cytometry was employed to detect the apoptosis of H9c2 cells. The interaction between HOTAIR and miR-17-5p was determined by bioinformatics analysis, luciferase reporter gene analysis, and RNA immunoprecipitation experiments. STAT3 and p-STAT3 expressions were detected by Western blot.Results: PPF pre-treatment significantly reduced creatine kinase isoenzyme (CK-MB) and serum lactate dehydrogenase (LDH) levels in the serum of the rats with MIRI. PPF pre-treatment remarkably up-regulated HOTAIR expression and down-regulated miR-17-5p expression in both in vivo and in vitro models. HOTAIR adsorbed miR-17-5p to repress the expression of miR-17-5p. PPF pre-treatment markedly inhibited cardiomyocyte apoptosis induced by I/R or H/R. HOTAIR knockdown could partially reverse the protective effects of PPF on MIRI. HOTAIR could activate STAT3 signaling via repressing miR-17-5p expression.Conclusion: PPF protects the MIRI by modulating the HOTAIR/miR-17-5p/STAT3 axis.Keywords: PPF, HOTAIR, miR-17-5p

Keywords

• ppf
• hotair
• mir-17-5p