Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6

Abstract Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. We applied in vivo rat model as well as in vitro cardiomyocyte models (H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial I/R injury. Next, transcriptomic sequencing was performed to determine the global change of gene expression and identified genes related to fatty acid metabolism were significantly regulated by Dex. Furthermore, shRNAs targeting Elovl6 were transfected into H9c2 cells and NRCMs to knockdown Elovl6. By comparing the effects of Dex on both wild type and Elovl6-knockdown cell under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, the protection efficiency of Dex was lower supported by the dataset including the cytotoxicity endpoints (cell viability and LDH release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays the key role in the process, which was further confirmed using palmitate exposure in both cells. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provide better understanding of the role of fatty acid metabolism in the function of Dex.