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

Abstract

Background

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

Acknowledgments

We thank Hubei Yican Health Industry Co., Ltd. for its linguistic assistance during the preparation of this manuscript.

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethics Statement

Our study was approved by the China-Japan Union Hospital of Jilin University (Approval number: 20190107C007).

Disclosure

The authors declare that they have no competing interests.