Effects Of Repeated Exposure To Propofol On Hippocampal Neuronal Apoptosis And Long-term Spatial Learning And Memory Ability In Neonatal Rats

Objective:To investigate the effects of repeated exposure to propofol on hippocampal neuronal apoptosis and long-term spatial learning and memory ability in neonatal rats.Methods:A total of 112 male newborn 7-day old Sprague-Dawley(SD)rats were randomly divided into 8 groups(n=14).Group control1(Con1),the rats in Con1 group received 0.9% saline intraperitoneal once per day for five days.Group P50,P100 and P150 respectively received propofol 50mg/kg,100mg/kg and 150mg/kg once per day for five days.Group control 2(Con2),the rats in Con 2 received 0.9% saline intraperitoneal once per day for five days,and appendectomy was performed under propofol anesthesia for the last day.Group SP50,SP100 and SP150 received propofol50mg/kg,100mg/kg and 150mg/kg r respectively once per day for five days and appendectomy was performed under propofol anesthesia for the last day.All 8 groups of rats were tested in Morris water maze behavioral experiments after 2 months.At the end of the experiment,the hippocampal formation of the fifth segment of the rat brain was taken,and the expression of Caspase-3,Bax(the pro apoptotic protein)and Bcl-2(inhibitor of apoptosis proteins)in hippocampus was determined by immunohistochemistry.The rest brain tissue homogenate was prepared in 10%,then supernatant was collected to determinate the IL-1,TNF-a,IL-6,IL-10,levels by protein suspension chip method.Results:Compared with Group control1(Con1),the expression of Caspase-3 and Bax in Group P50,P100 and P150 increased and the expression of Bcl-2 gradually decreased in group P50(p<0.05).Compared with the P50 group,the expression of Caspase-3 and Bax increase(p<0.05),and the expression of Bcl-2 decreased in Group P100 and P150.Compared with Group control 2(Con2),the expression of Caspase-3 and Bax gradually increased and the expression of Bcl-2 decreased gradually in group SP50,SP100 and SP150(p<0.05).Compared with the SP50 group,the expression of Caspase-3 and Bax increased and the expression of Bcl-2 decreased in group SP100 and SP150(p<0.05).In the Morris water maze test,compared with the Group control1(Con1),the escape latency prolonged gradually in group P50,P100 and P150(p<0.05),and no significant differences appeared in the times acrossd the platform in Group P50(p>0.05),and decreased in group P100 and P150(p<0.05).Compared with the Group control2(Con2),the escape latency had no significant difference in Group SP50(p>0.05),the escape latencies prolonged apparently in group SP100 and SP150(p<0.05).Compared with the group SP50,the escape latencies apparently prolonged in group SP100 and SP150(p<0.05).Compared with the Group control 2(Con2),no significant differences appeared in the times acrossd the platform in Group SP50(p>0.05),and decreased in Group SP100 and SP150(p<0.05).Compared with the Group control1(Con1),The level of TNF-?,IL-1?,IL-6 and IL-10 were increased in Group P50,P100 and P150.Compared with the Group control 2(Con2),The level of TNF-?,IL-1?,IL-6and IL-10 increased in Group SP50,SP100 and SP150.Conclusion:Repeated use of propofol can promote the apoptosis of hippocampal neurons of neonatal rats,the long-term spatial learning and memory ability will damage in a dose-dependent toxicity.