Phosphorylated CAMP Response Element-binding Protein In Gender Difference On The Effect Of Sevoflurane On Learning And Memory Between Male And Female Rats

Objective:To observe the gender difference in the effect of sevoflurane inhalation on learningand memory changes in adult rats, and phosphorylated CREB1protein-mediatedtranscription of apoptosis protein expression in hippocampus neurons after sevofluraneanesthesia, and to explore the possibility mechanism of sevoflurane on learning andmemory of adult rats.Methods:Sixty-four SD rats (32female,32male) that exhibited normal spontaneous activityand behaved normally in passive avoidance and Morris water maze tests, and30femaleand28male rats were be used in this study. They were divided into4groups: control groupfemale (Fc group), control group male (Mc group), sevoflurane group female (Fs group)and sevoflurane group male (Ms group). The control groups inhaled O2for2h, whilesevoflurane groups were anesthetized with3%sevoflurane in O2for2h. The spontaneousactivity test was performed at1,30,60and90d after sevoflurane anesthesia. While thepassive avoidance task was performed at2,30,60and90d after sevoflurane anesthesia.Morris water maze test was performed for5consecutive days at3~7d,31~35d,61~65dand91~95d after sevoflurane anesthesia. p-CREB1, Bcl-2, Caspase-8and Caspase-3protein expression in hippocampus were be observed by Western blot at7d and95d.Results:In spontaneous activity test the total distance and the speed were significantlydecreased at1d after sevoflurane anesthesia in both Fs and Ms groups as compared with Fc and Mc groups. There was no significant difference in the latency and number of errorafter sevoflurane anesthesia compared with the control groups in both male and female ratsin the passive avoidance task. In Morris water maze test, the escape latency and swimmingdistance were significantly prolonged at3d and31d after sevoflurane anesthesia ascompared with control group in female rats and at3~6d,31~34d and61d aftersevoflurane anesthesia as compared with control group in male rats, and were significantlylonger after sevoflurane anesthesia in male than in female rats. The significantlydown-regulated protein p-CREB1and Bcl-2and up-regulated protein Caspase-8andCaspase-3expression in both Fs and Ms groups as compared with Fc and Mc groups, whilep-CREB1and Bcl-2protein expression was higher in Fs group as compared with Ms groupafter sevoflurane anesthesia at7d. There was no significant difference on protein p-CREB1,Bcl-2, Caspase-8and Caspase-3expression in both Fs and Ms groups as compared with Fcand Mc groups after sevoflurane anesthesia at95d.Conclusion:Inhalation of3.0%sevoflurane for2h resulted in learning and memory impairmentsof adult female rats in31d and male rats in61d, and had a reversible impact of learningand memory in rats. And the mechanism of impairments may be inhibited p-CREB1expression, and decreased the expression of p-CREB1-mediated the protein Bcl-2, andincreased Caspase-8and Caspase-3protein expression in hippocampal neurons of adultrats, which promote hippocampal neuronal apoptosis.