ABSTRACT
Objective To evaluate the changes in 5'-adenosine monophosphate-activated protein kinase (AMPK) signal transduction pathway in hippocampal neurons of aged rats during transient global cerebral ischemia/reperfusion (I/R).Methods Ninety-six aged male Sprague-Dawley rats aged 18-22 months,weighing 450-600 g,were randomly allocated to one of two groups (n=48 each):sham operation group (group OS) and transient global cerebral I/R group (group OTIR).Ninety-six yong male Sprague-Dawley rats aged 3 months,weighing 200-250 g,were randomly divided into 2 groups (n=48 each):sham operation group (group AS) and transient global cerebral I/R group (group ATIR).The global cerebral I/R was produced by 3 min four-vessel occlusion followed by reperfusion according to Pulsinelli.On 3,5 and 7 days of reperfusion,12 rats in each group were chosen and sacrificed.Their brains were removed and hippocampal CA1 region was dissected for detection of neuronal apoptosis (by TUNEL) and expression of phosphorylated AMPKα (p-AMPKα) (by Western blot).The apoptotic rate (AR) was calculated.Results Compared with OS group,the AR was significantly increased and the expression of p-AMPKα was up-regulated at each time point in OTIR group,and the AR was significantly decreased and the expression of p-AMPKα was down-regulated at each time point in AS group (P ＜ 0.05).Compared with AS groupthe AR was significantly increased at each time point and the expression of p-AMPKα was up-regulated on day 3 and 5 of reperfusion in ATIR group (P ＜ 0.05).The AR was significantly lower at each time point and the expression of p-AMPKα was down-regulated on day 5 and 7 of reperfusion in ATIR group than in OTIR group (P ＜ 0.05).Conclusion Transient global cerebral I/R can activate AMPK signal transduction pathway in hippocampus of aged rats.The activation of AMPK signal transduction pathway is stronger and the cerebral I/R injury is more severe in aged rats than in young rats.