Reduced Mitochondria Response Sensitivity Is Involved In The Inhibition Of ROS-induced Apoptosis In Cardiomyocytes Pretreated With Dexmedetomidine

Objective:To observe apoptotic effect of dexmedetomidine pretreatment in cardiomyocytes and investigate the possible mechanisms.Methods:The present study used dexmedetomidine preincubated neonatal rat cardiomyocytes,and the rate of apoptosis was detected by using live cell observation,TUNEL staining and fluorescence-activated cell sorting（FACS）following hydrogen peroxide（H₂O₂）stimulation.To investigate dexmedetomidine-associated mitochondrial function,western blotting detected mitochondrial respiratory complexes,tetramethylrhodamine ethyl ester（TMRE）assay detectedΔψ_m,MitoSOX assay detected ROS production and flux analyzer detected cellular oxygen consumption rate（OCR）.Results:In the present study,it was demonstrated that dexmedetomidine pretreatment on primary cultured rat cardiomyocytes protected against reactive oxygen species（ROS）-induced apoptosis.In terms of the potential mechanism,it was demonstrated that dexmedetomidine inhibited mitochondrial biogenesis and mitochondrial respiratory complexes,but with increased coupling efficiency.However,dexmedetomidine upregulated mitochondrial membrane potential（Δψ_m）and resisted against the loss ofΔψ_m induced by carbonyl cyanide-p-trifluoromethoxy phenylhydrazone.The present study investigated the dexmedetomidine-suppressed mitochondrial response to H₂O₂stimulation,which was explained by suppressed ROS levels and the suppression of the increased oxygen consumption rate.Conclusion:Results demonstrated for the first time,to the best of our knowledge,a novel protective mechanism for dexmedetomidine on cardiomyocytes through the attenuated response of mitochondria towards H₂O₂,which had a protective effect against ROS-induced apoptosis.