Effect of dexmedetomidine on mitochondrion-dependent apoptosis during hypoxia-reoxygenation injury to hippocampal neurons of rats

Objective To evaluate effect of dexmedetomidine on mitochondrion-dependent apoptosis during hypoxia-reoxygenation (H/R) injury to hippocampal neurons of rats. Methods The primarily cultured hippocampal neurons of Sprague-Dawley rats were divided into 4 groups (n=40 each) using a random number table method: control group (C group), vehicle group (V group), H/R group and dexmedetomidine group (D group). Hippocampal neurons were subjected to oxygen-glucose deprivation followed by restoration of oxygen supply to establish the model of H/R injury.Dexmedetomidine 1 μmol/L was added at 6 h of reoxygenation in D group.The viability of neurons was measured by methyl thiazolyl tetrazolium assay at 20 h of reoxygenation.The ultrastructure of mitochondria was observed by transmission electron microscopy.The expression of cytochrome c (Cyt c), caspase-3, Fis1 and Drp1 was detected by Western blot.The neuronal apoptosis was detected by flow cytometry, and apoptosis rate was calculated. Results Compared with C group, no significant change was found in the viability of neurons in group V (P>0.05), and the viability of neurons was significantly decreased, the apoptosis rate was increased, the expression of Cyt c, caspase-3, Fis1 and Drp1 was up-regulated (P<0.05), and the damage to mitochondrial ultrastructure was accentuated in H/R and D groups.Compared with H/R group, the viability of neurons was significantly increased, the apoptosis rate was decreased, the expression of Cyt c, caspase-3, Fis1 and Drp1 was down-regulated (P<0.05), and the damage to mitochondrial ultrastructure was significantly attenuated in D group. Conclusion The mechanism by which dexmedetomidine reduces the H/R injury to hippocampal neurons is related to inhibiting mitochondrion-dependent apoptosis in rats. Key words: Dexmedetomidine; Anoxia; Mitochondria; Hippocampus; Neurons