Role of hippocampal PI3K∕Akt signaling pathway in exogenous orexin A-induced improvement of isoflurane anesthesia-caused decline in memory function of mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of hippocampal phosphatidylinositol 3-kinase∕serine-threonine kinase (PI3K∕Akt) signaling pathway in exogenous orexin A-induced improvement of isoflurane anesthesia-caused decline in memory function of mice. Methods A total of 100 pathogen-free healthy adult male C57BL∕6 mice, aged 8-12 weeks, weighing 20-25 g, in which the lateral ventricle was catheter-ized, were divided into 5 groups (n = 20 each) using a random number table control group (group C), isoflurane group (group I), orexin A group (group OA), orexin A plus dimethyl sulfoxide group (group OA+D) and orexin A plus PI3K inhibitor LY294002 group (group OA+LY). Normal saline was administra-ted in group C and group I. Orexin A 1. 5 mmol∕L was given in group OA. Orexin A 1. 5 mmol∕L (dissolved in dimethyl sulfoxide) was given in group OA+D. Orexin A 1. 5 mmol∕L and LY29400210 mmol∕L were given in group OA+LY. Group C only inhaled pure oxygen for 2 h (oxygen flow rate 2 L∕min), all the rest groups inhaled 1. 4％ isoflurane for 2 h, and the corresponding drug 2 μl was injected into the lateral cere-bral ventricle according to the concentration mentioned above at 15 min before the end of anesthesia. Twelve mice were randomly selected from each group and trained for contextual fear conditioning test, and then fear memory retrieval was conducted at 24 h after training. The rest 8 mice in each group were sacrificed at 2 h after the end of anesthesia and their brains were removed for determination of the expression of PI3K, Akt and phosphor-Akt (p-Akt) protein by Western blot. Results Compared with group C, the freezing time was significantly shortened, the expression of PI3K, Akt and p-Akt was down-regulated, and p-Akt∕Akt ratio was decreased in group I (P<0. 05). Compared with group I, the freezing time was significantly pro-longed, the expression of PI3K, Akt and p-Akt was up-regulated, and p-Akt∕Akt ratio was increased in group OA (P<0. 05). There was no significant difference in each parameter mentioned above between group OA and group OA+D (P>0. 05). Compared with group OA+D, the freezing time was significantly short-ened, the expression of PI3K, Akt and p-Akt was down-regulated, and p-Akt∕Akt ratio was decreased in group OA+LY (P<0. 05). Conclusion Hippocampal PI3K∕Akt signaling pathway is involved in exoge-nous orexin A-induced improvement of isoflurane anesthesia-caused decline in memory function of mice.