Objective Perioperative neurocognitive impairment(PND)is a common central nervous system disease caused by anesthesia in elderly patients.The incidence is high and the mechanism is not clear.Sevoflurane is a kind of inhaled anesthetic,which has the characteristics of rapid induction and stable hemodynamics.Sevoflurane is often used in clinical anesthesia,especially in elderly patients.Sevoflurane is more likely to cause PND than sedatives such as intravenous or other inhaled anesthetics.Signal transduction is a hot topic in life science.Different signal transduction pathways are independent and related to each other.In this study,we established an animal model of PND to explore the role of Ca MKIV / CREB/BDNF signal pathway in the pathogenesis of PND.Methods Thirty healthy male Sprague-Dawley rats,aged 18-20 months,weighing600-750 g were randomly divided into two groups: control group(group C)and experimental group(group E).Rats in group C inhaled 50% air and oxygen mixture for 4 hours,and rats in group E inhaled 3% sevoflurane and air oxygen mixture for 4hours.The function of the rats was measured by Morris water maze test,the location navigation test was performed 6 days before anesthesia and 1 day after ether inhalation,the escape latency and the total swimming distance were recorded,and the space exploration test was performed on the 6th day before and 1 day after ether inhalation to record the times of passing through the original platform and the time of movement in the second quadrant within 90 seconds.At the end of Morris water maze test,the rats were sacrificed on the 1st,3rd and 7th day after ether inhalation,and the brains were removed.The expression levels of Ca MK Ⅳ,CREB and BDNF in hippocampus were determined by Western blot method,and the m RNA expression levels of Ca MK Ⅳ,CREB and BDNF in hippocampus were measured by RT-PCR method.Results Compared with the 6th day of training,the escape latency and total swimming distance in group E were prolonged on the 1st day after inhaling ether,but there was no significant difference in group C on the 1st day after ether inhalation(P< 0.05).Compared with group C,the escape latency and total swimming distance in group E were longer on the first day after ether inhalation,while the crossing times and staying time in the original platform quadrant were decreased in group E(P <0.05).Compared with group C,the expressions of Ca MK Ⅳ,CREB and BDNF in group E were down-regulated on the 1st,3rd and 7th day after ether inhalation,and the expressions of Ca MK Ⅳ,CREB and BDNF in hippocampus in group E were significantly lower than those in group C on the 1st,3rd and 7th day after ether inhalation.Conclusion The occurrence of PND may be related to the inhibition of Ca MK Ⅳ /CREB/BDNF signal pathway in hippocampus. |