Objective To evaluate the effects of dexmedetomidine on lidocaine-induced apoptosis in rat cortical neurons.Methods The cortical neurons obtained from Sprague-Dawley fetal rats were seeded in 24 multiwell plates at a density of 1 × 105 cells/ml,and the cortical neurons of 80 wells were randomly divided into 4 groups (n =20 each):control group (group C),lidocaine group (group L),dexmedetomidine group (group D) and lidocaine + dexmedetomidine group (group L+ D).The cells were cultured routinely in group C.The cells were exposed to lidocaine with a final concentration of 1 mmol/L in group L.The cells were exposed to dexmedetomidine with a final concentration of 3 μmol/L in group D.The cells were exposed to lidocaine and dexmedetomidine with the final concentrations of 1 mmol/L and 3 μmol/L,respectively,in group L + D.After 4 h incubation,the neurons were subjected to DAPI staining for detection of apoptosis,and the apoptosis rate was calculated.Western blot analysis was used to measure the expression of phosphorylated Akt (p-Akt),Akt and caspase-3.Results Compared with group C,the apoptosis rate was significantly increased,the expression of p-Akt was down-regulated,and the expression of caspase-3 was up-regulated in L and L + D groups (P ＜ 0.05),while no significant changes were found in the indexes mentioned above in group D (P ＞ 0.05).Compared with group L,the apoptosis rate was significantly decreased,the expression of p-Akt was up-regulated,and the expression of caspase-3 was down-regulated in L + D group (P ＜ 0.05).There was no significant difference in the expression of Akt between the four groups (P ＞ 0.05).Conclusion Dexmedetomidine can reduce lidocaine-induced apoptosis in rat cortical neurons,and activation of Akt may be involved in the underlying mechanism.