The Study Of Effects And Mechanism Of Propofol On Cognitive Function In The Developing Brain Of Rats

Objective: To investigate the effect of propofol on cognitive functionand the related mechanism of synaptic plasticity in the developing brain ofrats.Methods: Ninety male and female Sprague Dawley rats aged7daysweighing12-16g were randomly divided into three groups （n=30）: Controlgroup （group C）,single propofol group （group P₁） and multiple propofolgroup（group P₂）. Group C were intraperitoneally received0.9%normalsaline （NS）7.5mL·kg^-1·d^-1for7d; group P₁were intraperitoneally receivedNS7.5mL·kg^-1·d^-1for6d and injected propofol75mg·kg^-1on the d7; groupP₂were intraperitoneally given propofol75mg·kg^-1·d^-1for7d. Fifteenminutes after the last intraperitoneal injection,6rats were marked thepuncture point of left ventricular in each group and blinded puncture to get100μl artery blood for blood gas analysis and glucose determination. Theother rats were subjected to Morris water maze to access spatial learningand memory function at age of28d and decapitated immediately after thetests. The CA1region of hippocampal of8rats in each group was isolated and sliced for recording of the field excitatory postsynaptic potential（f-EPSP） and the inducted rate of long-term potentiation （LTP） usingelectric physiology methods. The expressions of CaMKIIα andphosphorylated CaMKIIα （pCaMKIIα） in hippocampus CA1region weredetermined by immunochemistry and Western bolt.Results:1. During anesthesia SpO2and blood glucose were no obviouslydifferences, blood gas were in normol range among three groups （P>0.05）.2. When neonatal rats grow to infancy, rats of the cognitive functionwere no obviously difference in group C and P₁（P<0.05）. Compared withC and P₁group, the escape latency were significantly prolonged （P<0.05）,while the space exploration time were shorted in P₂group （P <0.05）.3. LTP detection results showed that3group the slope of f-EPSP andthe production rate of LTP were no obviously difference before the highfrequency stimulation among three groups（P>0.05）. Compared with Cgroup, after the high frequency stimulation the slope of f-EPSP were lowerslightly than that in group P₁（P<0.05）.The production rate of LTP was nodifferences between group C and P₁（P>0.05）. However, both the slope off-EPSP and the production rate of LTP were significantly reduced in P₂group （P<0.05）.4. Immunochemistry and Western bolt results revealed that theexpressions of CaMKIIα and pCaMKIIα also reduced and the ratio of pCaMKIIα/CaMKIIα decreased in group P₂compared with that of group C（P<0.05）. However, there were no obvious differences between group Cand P₁（P>0.05）.Conclusion:1. Exposure of the developing brain of rats to propofol causes descendthe slope of f-EPSP to some degree in the hippocampus CA1region.However, compared with that of single propofol group, the slope of f-EPSPwere lower than that in multiple propofol group. Moreover, propofolrepeated anesthesia significantly decreases the inducted rate of LTP in thedeveloping brain of rats.2. Multiple anesthesia by propofol induces the expression of CaMKIIαand pCaMKIIα significantly declinded in the developing brain of rats.3. Our findings indicate that propofol repeated anesthesia lead to reducethe cognitive function in the developing brain of rats, which may beassociated with inhibited the formation of LTP in hippocampal CA1regionand down-regulated expression of CaMKIIα and pCaMKIIα.