| Objective: To observe the effects of ICS?on the cognitive function and the expression of GSK3?,p-GSK3?,CREB,p-CREBand BDNF in hippocampus of chronic cerebral hypoperfusion rats in oder to explore the possible molecular mechanism and to provide experimental evidence for ICS?treatment of chronic cerebral hypoperfusion cognitive dysfunction.Methods: 90 male SD rats were randomly divided into normal group,sham operation group,model group,ICS?low,medium and high dose group.Chronic cerebral hypoperfusion model was established by ligated bilateral common carotid artery(2VO).The rats which were in ICS ? low,medium and high dose groups were continuously administered with ICS?4,8,16 mg / kg.d and which were in sham operation group and model group dministered with isodose saline respectively.Normal group without any treatment.The escape latency(s)and target quadrant residence were measured by water maze test at 4 and 8 weeks.The expression of GSK3?,p-GSK3?(Ser9),CREB,p-CREB(Ser133)and BDNF were assayed by immunohistochemistry.The average optical density was calculated by Image-Pro Plus 6.0.Results: Compared with normal group and sham operation group,the escape time and target quadrant residence time were significantly prolonged and shortened,the expression of GSK3? and p-GSK3?(Ser9),p-CREB(Ser133)and BDNF in hippocampal CA1 region were increased decreased respectively(P<0.05)in model group.Compared with model group,all indexs had no significant change(P>0.05)in the low dose group,but escape time and target quadrant residence time of rats were significantly prolonged and shortened and the expression of p-GSK3?(Ser9),p-CREB(Ser133)and BDNF were significantly increased and GSK3? was significantly decreased respectively(P <0.05)in medium and high dose groups Compared with 4 week,t,there was no significant change in 8 week in the same groups(P> 0.05).Conclusion: ICS ? can improve the spatial learning and memory ability of chronic cerebral hypoperfusion rats,which may be related to its inhibition of GSK3? protein expression,promotion expression of p-GSK3?,p-CREB and BDNF. |
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