Overexpression of Long noncoding RNA Oprm1 Attenuates Myocardial Ischemia/Reperfusion Injury by Increasing Endogenous Hydrogen Sulfide Production via Oprm1/miR-30b-5p/CSE axis

Abstract

Background: Ischemia/Reperfusion (I/R) Injury largely limits the efficacy of revascularization in acute myocardial infarction. Long noncoding RNA (lncRNA) Oprm1 is protective in cerebral I/R injury. However, the effect of lncRNA Oprm1 on myocardial I/R injury and its mechanism remains unknown.Methods: We ligated and then released the left anterior descending coronary artery of adult male rats to build the I/R model in vivo, while an H9c2 cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, histology, Tunnel staining, cell viability, and vital protein expression was conducted and compared.Results: lncRNA Oprm1 was significantly down-regulated in the I/R injury model. When administered with the AAV9-Oprm1 vector, the myocardial injury and cardiac function were mitigated and preserved, with apoptosis reduced. The cystathionine-γ-lyase (CSE) expression and hydrogen sulfide (H2S) expression were increased. The dual-luciferase reporter gene revealed the targeted relationship between lncRNA Oprm1 and miR-30b-5p. In H9c2 cardiomyocytes models, the miR-30b-5p blocked the protective effect of lncRNA Oprm1 on H/R injury, when Bcl-2, Bcl-xl was down-regulated, and HIF-1α, Bnip-3, Caspase-3, and Caspase-9 up-regulated.Conclusions: lncRNA Oprm1can competitively combines with miR-30b-5p, which down-regulates the expression of CSE. When administered with lncRNA Oprm1, increased endogenous H2S can reduce apoptosis and protect the myocardium from I/R injury via activating PI3K/Akt pathway and inhibiting HIF1-α activity.