Abstract: Objective To investigate the effect of FPS-ZM1 on isoflurane anesthesia induced cognitive dysfunction in aged rats. Methods Sixty aged rats were randomly divided into four groups(n=15)as follow: NS+O2、NS+ISO、FPS-ZM1+ISO、FPS-ZM1+O2.The NS+O2 and NS+ISO groups received intracerebroventricular injection of normalsaline 10 μL. The FPS-ZM1+O2 and FPS-ZM1+ISO groups received intracerebroventricular injection of FPS-ZM1 10 μL(5 g/L). 24 hours after intracerebroventricular injection, The NS+O2 and FPS-ZM1+O2 groups inhaled a gas mixture of oxygen and air for 4 h, and the NS+ISO and FPS-ZM1+ISO groups inhaled 2% isoflurane for 4 h. The tests of learning and memory were performed in Morris water maze, RAGE and amyloid β protein(Aβ) expression in hippocampus CA1 area was determined by immunohistochemistry. Results Compared with NS+ISO group, the escaping latency significantly shortened from 1 to 4 day, and the probe time was significantly increased, the time of staying at the original platform quadrant was significantly longer inthe FPS-ZM1+ISO group. In addition, the level of RAGE and Aβ expression of groups FPS-ZM1+ISO in hippocampus CA1 area was significantly reduced. Conclusion FPS-ZM1 may improve the process of spatial learning and memory by inhibiting Aβ expression in hippocampus CA1 area of aged rats.

Key words: FPS-ZM1, RAGE inhibitor, Isoflurane, Cognition disorders, Aged