| Objective: Perioperative neurocognitive disorders(PND),including acute mental disorder and persistent cognitive impairment after operation,is a common complication of neurological dysfunction after anesthesia and surgery.If it is not improved in time,it may further develop into irreversible cognitive changes,and even develop into Alzheimer’s disease.Sevoflurane has become one of the most commonly used inhaled anesthetics in clinic,but its long-term and high concentration inhalation will damage the long-term emotional memory consolidation.At present,there is no clear conclusion on the mechanism of PND.The intracellular signal transduction system changes rapidly and can organically connect and integrate a large number of signals,which is the main research direction of the mechanism of PND.In this study,we established a sevoflurane anesthesia-induced PND rat model to detect the expression of brain-derived neurotrophic factor(Brain-derived neurotrophic factor,BDNF)and its specific receptor tyrosine protein kinase B(Tyrosine protein kinase receptor B,Trk B)in hippocampal neurons,and to explore the related molecular mechanisms affecting cognitive function.Methods: Forty-two aged SD rats were randomly divided into two groups: control group(group C)and experimental group(group S).The rats in group S inhaled 3%concentration of sevoflurane and air oxygen mixture for 4 hours,and the rats in group C inhaled 50% air and oxygen mixture for 4 hours.The aged rats of the two groups were subjected to Morris water maze test before and after anaesthesia respectively,and the success of the model was judged by analyzing the tracking data.After successful establishment of the model,the rats were killed at different time points,and the hippocampus was decapitated.The protein expression levels of BDNF,Trk B and p-Trk B in hippocampal tissue were determined by Western Blot method,and the m RNA expression levels of BDNF,Trk B and p-Trk B in hippocampal tissue were detected by Real-time PCR.Results: 1.The results of Morris water maze experiment showed that :(1)Compared with the 6th day of training,the escape latency and total swimming distance of rats in group S were prolonged after ether absorption,and the differences were statistically significant(P < 0.05).The escape latency and total swimming distance of rats in group C were not significantly different at 1 day after ether absorption(P >0.05).Compared with group C,the escape latency and total swimming distance of group S were prolonged after ether absorption,and the differences were statistically significant(P < 0.05).(3)Compared with the 7th day of training,the original platform crossing times and the original platform quadrant residence time of group S were reduced after ether absorption,and the difference was statistically significant(P < 0.05).The original platform crossing times and the original platform quadrant residence time of group C were not significantly different on 1 day after treatment(P > 0.05).Compared with group C,the number of original platform crossing and the quadrant residence time of original platform were reduced in group S after ether absorption,and the differences were statistically significant(P < 0.05).2.Western Blot and real-time PCR results showed that :(1)Compared with group C at the same time,the expression of BDNF in the hippocampus of rats in group S was significantly down-regulated on day 1 after ether absorption,and the phosphorylation expression of Trk B in the hippocampus BDNF signaling pathway was significantly down-regulated,with statistical significance(P<0.05).(2)The phosphorylation expression of BDNF and Trk B in the hippocampus was gradually upregulated on the 3rd and 7th day after anesthesia,and there were statistically significant differences in each index between the two groups on the 3rd day(P<0.05),while there were no statistically significant differences in each index between the two groups on the 7th day(P>0.05).Conclusion: 1.Inhalation of3% sevoflurane for 4h resulted in cognitive decline in elderly SD rats;2.The expression of BDNF decreased in the hippocampus of rats with cognitive impairment,and the phosphorylation activity of Trk B protein was inhibited.3.Sevoflurane-induced PND in elderly rats may be related to the inhibition of BDNF/Trk B signaling pathway in the hippocampus. |
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