AngⅣ-analog dihexa protects learning and memory abilities in neonatal rats undergoing repeated anesthesia with propofol
Objective To investigate the effect of pre-administration of angⅣ-analog Dihexa,on the learning and memory abilities of neonatal rats undergoing repeated anesthesia with propofol and its mechanism.Methods Seventy-eight Sprague-Dawley rats aged 7 days(body weight 12-20 g)were randomly divided into 3 groups(26 rats/group):control group,repeated propofol exposure(propofol)group,and Dihexa+repeated propofol exposure(Dihexa+propofol)group.Rats in control group were intraperitoneally injected with physiological saline(7.5 mL/kg),and the rats in propofol group were intraperitoneally injected with propofol(75 mg/kg).The rats in Dihexa+propofol group were first intraperitoneally injected with Dihexa(0.5 mg/kg),after 25 minutes,with propofol(75 mg/kg).The treatment lasted for 5 continuous days.At 24 hours after the last administration,some rats were sacrificed by cervical dislocation.Rat brain tissues were collected.ELISA was performed to detect the contents of angiotensin Ⅳ(Ang Ⅳ),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in rat hippocampal tissues.Western blot was used to detect the expressions of hippocampal synapsin(SYP)and postsynaptic density protein 95(PSD95).Golgi staining was used to observe the density of dendritic spines.Morris water maze experiment was performed on 8 rats aged 30 days selected from each group to evaluate their spatial learning and memory abilities.Results When compared with control group,propofol group had an increased escape latency period of 2-5 days,reduced number of platform crossings,a shortened target quadrant residence time,decreased Ang Ⅳcontent,increased IL-1β and TNF-α contents,reduced protein expressions of PSD95 and SYP in the hippocampal tissue and decreased density of dendritic spines in the hippocampal CA1 region(P＜0.05).When compared with propofol group,Dihexa+propofol group had shortened escape latency period of 2-5 days,increased number of platform crossings,a prolonged target quadrant residence time,increased Ang Ⅳcontent,decreased IL-1β and TNF-α contents,elevated protein expressions of PSD95 and SYP in the hippocampal tissue and increased density of dendritic spines in the hippocampal CA1 region(P＜0.05).Conclusion Dihexa preconditioning may inhibit hippocampal inflammatory response and synaptic plasticity damage induced by repeated propofol anesthesia in neonatal rats,thus protecting their learning and memory abilities.
neonatal ratspropofolangiotensin Ⅳ analogueinflammatory responsesynaptic plasticitylearning and memory abilities
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