Effects of dexmedetomidine on developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy

Objective:To investigate the effects of developmental damage of hippocampal neurons in offspring rats induced by sevoflurane inhalation anesthesia during pregnancy and its related mechanisms.Methods:Eighteen pregnant female Sprague-Dawley(SD)rats were randomly divided into three experimental groups:the control group(intraperitoneal injection of 0.9%sodium chloride solution 100 mL),the sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of 0.9%sodium chloride solution 100 mL),and the dexmedetomidine combined with sevoflurane inhalation anesthesia group(inhalation of 1 MAC sevoflurane for 6 h and intraperitoneal injection of dexmedetomidine 100 mL),with 6 rats in each group.On the day of birth,the offspring rats of each experimental group were randomly selected.And blood gas analysis was performed with left ventricular artery blood of each offspring.The expression of cleaved-caspase-3 in hippocampal neurons was measured by Western blot.The mRNA expressions of growth-associated protein-43(GAP-43)and neuronal nitric oxide synthase(nNOS)in hippocampus of offspring rats were detected by real-time RT-PCR.The protein expressions of GAP-43 and nNOS were tested by immunohistochemistry and Western blot.Results:Compared with the control group,cleaved-caspase-3 expression in hippocampal neurons of offspring rats in sevoflurane inhalation anesthesia group increased significantly.Cleaved-caspase-3 in hippocampal neurons of offspring after dexmedetomidine combined with sevoflurane inhalation anesthesia was dramatically lower than that in sevoflurane inhalation anesthesia group.Compared with the sevoflurane inhalation anesthesia group,dexmedetomidine combined with sevoflurane inhalation anesthesia could markedly up-regulate the mRNA and protein expressions of GAP-43 and nNOS.Conclusion:Dexmedetomidine can protect hippocampal neurons from developmental damage induced by sevoflurane inhalation anesthesia during pregnancy,which may be related to the up-regulation of the mRNA and protein expressions GAP-43 and nNOS.