Effect of atorvastatin preconditioning on cognitive function in isoflurane-anaesthetized mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of atorvastatin preconditioning on cognitive function in isoflurane-anaesthetized mice.Methods Forty-eight healthy male C57BL/6 mice,aged 3 months,weighing 27-41 g,were divided into 3 groups (n =16 each) using a random number table:control group (group C),isoflurane anesthesia group (group Ⅰ) and atorvastatin preconditioning plus isoflurane anesthesia group (group AI).Atorvastatin 10 mg/kg was given through a gastric tube into the stomach at the same time every day for 7 consecutive days in group AI.In Ⅰ and AI groups,1.5％ isoflurane was inhaled for 6 h with fresh gas flow of 2 L/min at 1 day after the end of administration.Open field test and Morris water maze test were performed at 1 day after the end of anesthesia.The mice were sacrificed at 1 day after the end of Morris water maze test,and hippocampi were isolated for determination of caspase-3,Bax and Bcl-2 expression (by Western blot) and contents of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α) and soluble Aβ1-42 in hippocampal tissues (by enzyme-linked immunosorbent assay).Results There was no significant difference in the parameters of open field test among the three groups (P＞0.05).Compared with group C,the escape latency was significantly prolonged at each time point,the time of staying at the original platform quadrant was shortened,the frequency of crossing the original platform was decreased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were increased,the expression of caspase-3 and Bax was up-regulated,and Bcl-2 expression was down-regulated in Ⅰ and AI groups (P＜0.05).Compared with group Ⅰ,the escape latency was significantly shortened at each time point,the time of staying at the original platform quadrant was prolonged,the frequency of crossing the original platform was increased,the contents of IL-1β,TNF-α and soluble Aβ1-42 were decreased,the expression of caspase-3 and Bax was downregulated,and Bcl-2 expression was up-regulated in group AI (P＜0.05).Conclusion Atorvastatin preconditioning can improve cognitive function in isoflurane-anaesthetized mice,and the mechanism may be association with attenuating hippocampal inflammatory responses,inhibiting over-expression of Aβ1-42 and inhibiting neuronal apoptosis.