The Effect And Mechanism Of ZL006 On Sevoflurane-induced Short-term Memory Retrevail Dysfunction Of Adult Mice

Objective:To observe the effect of ZL006 on short-term memory retrevail dysfunction of adult mice induced by sevoflurane,and to investigate the possible mechanism of sevoflurane-induced impairment of short-term memory retrieval of adult mice.Methods:24 healthy adult Kunming mice,aged 2 months,half male and half female,weighing 30-35g,were randomly divided into three groups:sevoflurane group（group S）,sevoflurane+ZL006 group（group Z）and Oxygen group（group C）.Step-through training and the step-down training was carried out,and sevoflurane anesthesia was performed 24 hours after the establishment of passive avoidance memory.Half an hour before sevoflurane anesthesia,group Z was intraperitoneally injected with ZL006（1.0 mg/kg,ZL006 was dissolved into 0.1mg/ml with saline,and then injected intraperitoneally with 10ml/kg.）,group C and group S was intraperitoneally injected with the same volume（intraperitoneal injection of 10ml/kg）.24 hours after the successful establishment of dark memory,40%O₂+3.3%sevoflurane was inhaled in group S and group Z for 2 hours,40%O₂was inhaled in group C for 2 hours.At 12 hours after inhaling sevoflurane or oxygen,the latency and delta latency（Δlantency is the difference between the pre-and post-anesthesia in lantency.）and the error times in 5min were tested to evaluate the changes of passive evasion memory extraction ability of mice.After recording the incubation period and the number of errors in 5min,the mice were decapitated immediately.The hippocampal tissue was taken to detect the expression of PSD95 and n NOS protein by Western Blot method,and the interaction between PSD95 and n NOS protein was detected by immunoprecipitation method..Results:1.The results of step-through test:compared with group C,12 hours after inhalation of sevoflurane,the step-through latency of group Z and group S was shortened,theΔlatency and error times in 5min were increased（P<0.05）.compared with group S,12 hours after inhalation of sevoflurane,the step-through latency of group Z was prolonged,theΔlatency and error times in 5min were decreased（P<0.05）.2.Co-immunoprecipitation:Compared with group C,the co-expression of PSD95 and n NOS was up-regulated in group Z and group S at 12h after sevoflurane inhalation（P<0.05）.Compared with the group S,the co-expression of PSD95 and n NOS was down-regulated in the group Z at 12h after sevoflurane inhalation（P<0.05）.The results of Western Blot:compared with group C,there was no significant difference in PSD95 protein expression and n NOS protein expression 12 hours after administration with sevoflurane in group Z and group S（P>0.05）.compared with group S,there was no significant difference in PSD95 protein expression and n NOS protein expression 12 hours after administration with sevoflurane in group Z（P>0.05）..Conclusion:ZL006 can improve short-term memory retrevail dysfunction induced by sevoflurane of adult mice,and the mechanism of sevoflurane-induced short-term memory impairment of adult mice may be related to PSD95-nNOS.