Dexmedetomidine alleviates myocardial ischemia/reperfusion-induced injury and Ca2+ overload via the microRNA-346-3p/CaMKIId axis.

Abstract Myocardial ischemia/reperfusion (MI/R) may impair cardiac functions. Dexmedetomidine (DEX) is protective in various clinical cases. Therefore, this study investigated the role and mechanism of DEX in MI/R. The myocardial infarct size, apoptosis, and levels of myocardial enzymes, SOD, ROS, Ca2+, and inflammatory factors in DEX-treated MI/R rats were measured. Differentially expressed microRNAs (miRs) in DEX-treated MI/R rats were detected. miR-346-3p was intervened to assess the effects of DEX on MI/R rats. The targeted binding relationship between miR-346-3p and CaMKIId was predicted and verified. DEX effect on hypoxia/reoxygenation (H/R)-induced cell model was evaluated. The role of CaMKIId in DEX protection was assessed after CaMKIId overexpression in H/R cells. NF-κB pathway and NLRP3 inflammasome-related protein levels were detected. DEX alleviated the myocardial injury and Ca2+ overload in MI/R rats, as evidenced by reduced infarct size, apoptosis and levels of myocardial enzymes, ROS, Ca2+, and inflammatory factors. DEX promoted miR-346-3p expression in MI/R rats, and miR-346-3p knockdown reversed DEX protection on MI/R rats. miR-346-3p targeted CaMKIId. DEX improved H/R-induced cell injury and Ca2+ overload and inhibited NF-κB/NLRP3 inflammasome-related protein levels, which were all reversed by CaMKIId overexpression. DEX alleviated injury and Ca2+ overload in MI/R via regulating the miR-346-3p/CaMKIId axis and inhibiting the NF-κB/NLRP3 inflammasome pathway.