Dexmedetomidine interferes with sevoflurane-induced hippocampal damage in elderly diabetic rats
Objective To investigate the possible mechanism of cognitive dysfunction in sevoflurane-induced elderly diabetic rats with endotoxemia and the protective effect of dexmedetomidine on hippocampal tissue.Methods A total of 24 Sprague-Dawley(SD)rats with 20 weeks old and specific pathogen-free(SPF)level were divided into 4 groups,with 6 rats in each group,including blank control group(Group C),model control group(Group M),sevoflurane group(Group S),and dexmedetomidine combined sevoflurane group(Group S+D).Rats in Group C were not treated.Rats in other groups were subjected to the modeling of senile diabetic endotoxemia.Rats in Group S were anaesthetized with sevoflurane for inhalation,and those in Group M+S were injected with dexmedetomidine and then anaesthetized with sevoflurane.After successful modeling,cognitive function and neurobehavioral changes were observed.Hippocampal damage was detected by H&E staining.The expressions of endoplasmic reticulum stress(ERS)proteins were detected by Western blot.Results After sevoflurane anesthesia,the learning and memory ability,thermal sensitivity,spatial cognitive ability and exploration behavior were significantly impaired in Group S than those of Group M.However,the neurobehavioral indexes were improved in Group S+D(P＜0.05).The apoptotic protein Casepase-12 and ERS-related proteins glucose-regulated protein 78(GRP78),activating transcription factor 6(ATF6)and C/EBP Homologous Protein(CHOP)were significantly upregulated in Group S compared with those of Group M.They were significantly downregulated in Group S+D than those of Group S(P＜0.05).Conclusion Sevoflurane inhalation anesthesia can induce cognitive dysfunction and hippocampus injury in elder endotoxemia diabetic rats,which can be relieved by dexmedetomidine via mediating the ERS-ATF6-CHOP apoptosis pathway.
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