Effect of sevoflurane on hippocampal cAMP-PKA-CREB signaling pathway in aged rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of sevoflurane on hippocampal cyclic AMP (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in aged rats.Methods Sixty healthy aged male Sprague-Dawley rats,aged 18 months,weighing 600-750 g,were divided into control group (C group,n =30) and sevoflurane group (group Sev,n =30) using a random number table method.Group Sev inhaled 2％ sevoflurane for 4 h.Group C inhaled the mixture of 50％ air and oxygen (2 L/min) for 4 h.Morris water maze test was performed on 1-6 days before anesthesia and at 1 day after the end of anesthesia (at the corresponding time points in group C).The animals were sacrificed and hippocampi were removed at 1,3 and 7 days after anesthesia (at the corresponding time points in group C) for determination of the hippocampal cAMP content (using enzyme-linked immunosorbent assay) and expression of hippocampal CREB,phosphorylated CREB (p-CREB) and PKA (using Western blot),and the p-CREB/CREB ratio was calculated.Results Compared with group C,the escape latency and swimming distance were significantly prolonged,the frequency of crossing the original platform was decreased,the time of staying at the original platform quadrant was shortened at 1 day after the end of anesthesia,and the expression of hippocampal cAMP and PKA was down-regulated at 1,3 and 7 days after the end of anesthesia,and the expression of CREB and p-CREB was down-regulated and p-CREB/CREB ratio was decreased at 1 day after the end of anesthesia in group Sev (P＜ 0.05).Conclusion The mechanism of sevoflurane-induced postoperative cognitive dysfunction may be related to inhibiting hippocampal cAMP-PKA-CREB signaling pathway in aged rats.