Abstract:

Objective To explore the mechanism of A kinase anchor-protein 150 （AKAP150） in alleviating learning and memory impairment induced by propofol in rats at developmental stage. Methods 80 SD rats aged 7 days were randomly divided into a control group （Con group）， propofol group （Pro group）， dexmedetomidine pre-administration group （DP group）， and AKAP150 adenovirus plus DP group （ADP group） （n = 20）. The Con group was injected with equal volume normal saline. The Pro group was injected with propofol of 50 mg/kg twice， and the DP group was injected with dexmedetomidine of 25 μg/kg plus propofol of 50 mg/kg. The ADP group was treated with adenovirus to construct an AKAP150 knockout model. Expression levels of AKAP150， PKA， NLRP3， GSDMD， IL-1β and IL-18 in hippocampus were detected by Western blot. The ultrastructure of hippocampus was observed by transmission electron microscopy. Results After propofol treatment， hippocampal cell membrane split and pores formed， expressions of AKAP150 and PKA were down-regulated （P < 0.05）， while expressions of NLRP3， GSDMD， IL-1β and IL-18 were up-regulated （P < 0.05）， and the frequency of crossing the platform was decreased （P < 0.05）. After pre-administration of dexmedetomidine， the cell membrane structure of hippocampus was basically normal， expressions of AKAP150 and PKA were up-regulated （P < 0.05）， expressions of NLRP3， GSDMD， IL-1β and IL-18 were down-regulated （P < 0.05）， and the frequency of crossing the platform was increased （P < 0.05）. Conclusions Dexmedetomidine may enhance the activity of PKA and inhibit expressions of NLRP3， GSDMD， IL-1β and IL-18 by activating expression of AKAP150， thereby alleviating propofol-induced pyroptosis in hippocampal tissues and improving learning and memory impairment in rats at developmental stage.

Key words: dexmedetomidine, propofol, A kinase anchor protein 150, learning and memory, pyroptosis