Effects Of 5-HT₃Receptor Mediated CAMP-PKA-CREB Signaling Pathway On The Cognitive Function Of Sevoflurane-induced Aged Rats

Objective:By establishing a model of cognitive dysfunction in elderly Sprague-Dawley（SD）rats caused by inhalation of sevoflurane and observe the expression of 5-HT₃receptor,cAMP、PKA、CREB and p-CREB in hippocampal tissue of elderly SD rats was detected.In order to clarify the effect and mechanism of sevoflurane and 5-HT3 receptor on cognitive function of elderly SD rats,provides the oretical and experimental datas for the treatment and prevention of pocd.Methods:There were Sixty healthy SD rats,all male,18-20 months old,weighing 600-700g Divided into two groups by random number table method:Blank group（blank B,n=30）,Sevoflurane group（group S,n=30）.Group S received 50%air and oxygen mixed gas（2L/min）and 2%sevoflurane for 4h and waiting for the rats to recover naturally;Group B received 50%air and oxygen mixed gas（2L/min）for 4h thenreturned to the cage.In the experiment,sixty SD rats began the Morris water maze experiment 6 days before modeling,and the Morris water maze experiment was conducted again 1 day after modeling to record the original platform crossing times,the second quadrant residence time,escape latency and swimming distance of the elderly SD rats.Ten old rats were randomly selected on the first,third and seventh day after the model establishment.SD rats were anesthetized by intraperitoneal injection of chloral hydrate and killed.The hippocampus was obtained by stripping the brain tissue.The expression of 5-HT₃receptor in hippocampus was detected by real-time PCR,CREB,p-creb and PKA were detected by western blot,p-CREB/CREB was calculated,and the expression level of cAMP was determined by Elisa.Results:Through the analysis of zoological behavior,it was concluded that the swimming distance of SD rats in group S was significantly prolonged（p<0.05）and escape latency was prolonged（p<0.05）on the first day after anesthesia,the residence time in the second quadrant was shortened（p<0.05）,and the number of crossing times on the original platform was reduced（p<0.05）.On the third day after anesthesia,the evasive incubation period,swimming distance,and the second quadrant residence time gradually shortened,and the patient returned to normal.After 7 days of anesthesia,the evasive incubation period,swimming distance,and the second quadrant residence time were nearly normal（P>0.05）.In contrast B,the expressions of CREB,p-creb,PKA,cAMPand 5-HT₃receptors,in the hippocampus of rats in group S were down-regulated and the p-CREB/CREB ratio was decreased on the first day after anesthesia.The expressions of 5-HT₃receptors,CREB,p-CREB,PKA and cAMP in the hippocampus were gradually up-regulated on the third and seventh day after anesthesia,and the expressions on the seventh day were close to those in group C（P>0.05）.Conclusion:The occurrence of cognitive dysfunction induced by 2%sevoflurane in elderly SD rats may be related to the camp-pka-creb signaling pathway mediated by 5-HT₃receptor.