Dexmedetomidine and ketamine combined with anesthesia play an neuroprotective role in hippocampus of rats

JIANG Weirong; XU Yanbing; WANG Jingbo

doi:10.3969/j.issn.1002-266X.2017.28.006

Abstract：Objective To explore the protective effect of ketamine and dexmedetomidine combined with anesthesia on nerve cells in hippocampus of rats.Methods A total of 32 SD rats were randomly divided into the negative control group (NC group), ketamine (K) group, dexmedetomidine (D) group, and K+D group with 8 rats in each group.In the NC group, 50 mL/kg normal saline was injected intraperitoneally, and normal saline was injected subcutaneously after 5 min.In the ketamine group, 70 mg/kg ketamine was injected intraperitoneally, and normal saline was injected subcutaneously after 5 min.In the dexmedetomidine group, 50 mL/kg normal saline was injected intraperitoneally, and 25 μg/kg dexmedetomidine was injected subcutaneously after 5 min.In the K+D group, 70 mg/kg ketamine was injected intraperitoneally, and 25 μg/kg dexmedetomidine was injected subcutaneously after 5 min.The breathing rates, righting reflex time was recorded, the memory function of rats was measured by Morris water maze test at the moment of injection (t0), at the injection of 15, 30, 45, 60, 75, and 90 min (t1-t6).The rats were sacrificed after the administration, neuronal apoptosis in CA region was measured by TUNEL assay, and the expression of PKC, ERK1/2, and Bcl-2 protein was measured by Western blotting.Results Compared with the K+D group, the righting reflex disappeared time of the ketamine group was significantly prolonged, the sedation duration and righting reflex disappeared time was significantly shorter, the difference between the two groups was statistically significant (all P<0.05).The breathing rates of the ketamine group were significantly higher than those of the NC group, dexmedetomidine group, and K+D group at t1, t2, t3 (all P<0.05).There was no significant difference between NC group, dexmedetomidine group and K+D group in the escape latency of each period (all P>0.05).On the 4th and 5th days of training, the escape latency of the ketamine group was significantly longer than that of NC group, dexmedetomidine group and K+D group (all P<0.05).The neuronal apoptosis ratio of the ketamine group was significantly higher than that of NC group, dexmedetomidine group and K+D group (all P<0.05).The expression of p-PKC, p-ERK1/2, and Bcl-2 protein of the ketamine group was significantly lower than that of NC group, dexmedetomidine group and K+D group (all P<0.05).Conclusion Dexmedetomidine and ketamine combined with anesthesia have the protective effect on nerve cells in hippocampus of rats by the activation of PKC-ERK1/2-Bcl-2 signaling pathway.