Effect of nimodipine on DNA-binding activity of cAMP response element binding protein and CCAAT enhancer binding protein in hippocampus in vascular dementia rats / 中华行为医学与脑科学杂志

ABSTRACT

ObjectiveTo observe the effect of nimodipine on hippocampal DNA-binding activity change of cAMP response element binding protein ( CREB )and CCAAT enhancer binding protein (C/EBP) in a rat model of vascular dementia(VD),and to explore the treatment mechanism of nimodipine.Methods66 healthy adult male SD rats were assigned to the following three groups of 22 eachVD model group,Sham-operated group,Nimodipine group.VD rat model was prepared by four-vessel occlusion.Physiological saline solution( 8 ml · kg-1 · d-1 )and Nimodipine (20 mg· kg-1 · d-1 )were administered by gavage respectively.The Morris maze was adopted to detect the changes of spatial learning and memorizing capacity,while HE straining was adopted to observe the changes of pathological characteristics in hippocampal CA1 area,and electrophoretic mobility shift assay(EMSA) were adopted to observe DNA-binding activity changes of CREB and C/EBP in hippocampus tissue.ResultsThe Morris maze showedthe learning and memory ability of nimodipine group rats ( escape latency period ( 26.63 ± 1.31 )s,the times of cross-platform(7.25 ±0.92) times) was higher than that of VD model group(escape latency period (41.25 ± 1.83 ) s,the times of cross-platform ( 5.33 ± 0.64 ) times ),with difference of statistical significance (P ＜0.05).HE results:in VD model group,neurons in CA1 were scaltered and boundaries were unclear,nuclei region was stained,coagulation necrosis appeared,obviously cells lost.The CA1 neurons of nimodipine group returned to be normal,nuclear membrane's profile and nudeolus were clear,regularly arranged; the number of hippocampal normal neurons in nimodipine group (43.19 ± 2.87 ) was more than that of VD model group( 16.33 ± 1.09 ),with difference of statistical significance(P＜0.05 ).EMSAboth CREB and C/EBP DNA-binding activity in rat hippocampus of nimodipine group ( ( 369.75 ± 13.22 ),( 428.25 ± 17.69 ) respectively ) were higher than those of VD model group ( ( 142.25 ± 27.86 ),(97.00 ± 5.88 ),respectively),with difference of statistical significance (P ＜0.01 )).ConclusionNimodipine can improve VD rats hippocampal neuronal injuries and their learning and memory impairment may be involved in the upregulating CREB and C/EBP DNA-binding activity.