The Effect And Mechanism Of Propofol Anesthesia On Cognitive Outcome In Infant Rats Under Hypoxic Conditions

Objective:To investigate the effects and mechanisms of propofol anesthesia on cognitive outcome in newborn rats under hypoxic conditions.Methods:A total of 108 seven-day old Sprague Dawley?SD?rats were assigned into one of the six treatments:lipide mulsion solvent+50%oxygen?CO?,lipid emulsion solvent+air?CA?,lipid emulsion solvent+18%oxygen?CH?,propofol+50%oxygen?PO?,propofol+air?PA?,propofol+18%oxygen?PH?.Propofol?50 mg/kg?or lipid emulsion solvent?5.0 ml/kg?was intraperiotoneally administered to seven-day-old SD rats one time each day seven consecutive days.The respiratory rate?RR?and SpO₂ were monitored after administration.The rats were returned to the cage after recovery of right reflex.Learning and memory functions were assessed using Morris water maze at 28 days old of rats.Immunohistochemistry method was used to detect the expression of Cleaved-caspase-3 in hippocampus CA1 region.Caspase-3,Akt,phospho-Akt,GSK-3 beta and phospho-GSK-3 beta proteins were detected by Western blotting in the hippocampus at the end of exposure.Results:?1?RR and Sp O₂ results:RR,SpO2 were not statistically significant between the control groups?CO,CA,and CH?.Compared with the control groups,the RR of rats in the propofol groups?PO,PA,and PH?decreased?P<0.01?.Compared with control groups,the SpO₂ in PO group was not statistically different,the PA and PH groups decreased significantly?P<0.01?,and the hypoxia was obvious.?2?Water maze results:There was no significant difference in escape latency between the control groups?CO,CA,and CH?at day 1-5?P>0.05?.Compared with the control group,escape latency in PO groupwas significantly prolonged at DAY 4-5?P<0.01?,and there was no significant difference in the number of crossing platforms?P>0.05?.Compared with the control group,escape latency in PA and PH groups significantly prolonged at 2-5 days?P<0.01?,the number of crossing platforms decreased?P<0.05?,and the target quadrant retention time decreased?P<0.05?.Compared with the PO group,escape latency in PA group was prolonged at day 4-5?P<0.05?.Compared with the PO group,escape latency in PH group was significantly prolonged at day 2-5?P<0.01?,the number of crossing platform decreased?P<0.05?,and the target quadrant retention time decreased?P<0.05?.?3?Immunohistochemical results:Cleaved-caspase-3 was negative or slightly positive in each sample of the control groups or the PO group.Cleaved-caspase-3 in the PA group or PH group was positively or strongly positively stained.The semi-quantitative results showed that comparison between PO group and control groups,there were no significant difference in the number of positive cells or integral optical density?IOD?;Compared with the control groups,the number of Cleaved-caspase-3 positive cells and IOD in PA group or PH group increased significantly?P<0.05?.?4?Western blot results showed that compared with the control groups,the expressions of Caspase-3,p-Akt/Akt ratio or p-GSK-3?/GSK-3?ratio in PO group was not statistically significant.compared with the control groups,the expression of Caspase-3 was increased?P<0.05?,p-Akt/Akt ratio was statistically decreased?P<0.01?,and p-GSK-3?/GSK-3?ratio in PA group or PH group was statistically decreased?P<0.01?.Conclusion:?1?Propofol anesthesia caused significant respiratory depression.Under air or hypoxic conditions,SpO₂ was significantly reduced in rats and hypoxia was obvious.?2?Propofol anesthesia increase the neuronal apoptosis and cognition impairment in neonatal rats under air or mild hypoxic environment.In the environment with adequate oxygen supply?50%O₂?,no obvious apoptosis of nerve cells.?3?The neurotoxicity of propofol combined with hypoxia may be related to the inhibition of phospho-Akt and increased GSK-3 beta expression.