Effect of Minocycline on Hippocampal Neuroapoptosis and Cognitive Dysfunction in Aged Rats / 医药导报

ABSTRACT

Objective To investigate the effect of minocycline on isoflurane-induced hippocampal neuroapoptosis and cognitive dysfunction in aged rats. Methods Forty-five male SD rats were randomly assigned into 3 groups ( n=15) blank control group ( group C) , 1.5% isoflurane group ( group I) and 50 mg??kg-1 minocycline+1.5% isoflurane group ( group M+I) . Minocycline was injected intraperitoneally 12 h before the start of anesthesia for group M+I.Group I and group M+I were exposed to 1.5% isoflurane for 4 h, while group C were exposed to 30% O2-70% N2.At the end of anesthesia, five rats in each group were randomized to analyse arterial blood gas. The other rats in each group were sent back to their home cage until they were fully awake.Fourteen days after anesthesia, Morris water maze was used to assess the cognitive function, and then hippocampi of rats were dissected for detection of the expression of cleaved caspase3, Bax and Bcl-2. Results No difference was found in arterial gas analysis among the 3 groups (P>0.05).Compared with group C, the rats in the group I spent more time locating the platform on the third and fourth training days and the time percentage that the rats in group I spent in the target quadrant was much less (P<0.05).However, these changes were reversed in group M+I (P<0.05).The isoflurane-induced increased level of Bax and cleaved caspase3 and decline of anti-apoptotic factor Bcl-2 were restored by minocycline pretreatment ( P<0.05) . Conclusion Minocycline could attenuate cognitive dysfunction induced by isofluranein aged rats.The mechanism is associated with inhibition of hippocampal neuroapoptosis which is increased by isoflurane.