Effect Of Donepezil On Expression Of NF-κB,COX-2 And Neurons Apoptosis In The Hippocsampus CA1 Of Rats With Vascular Dementia

ObjectivesPrepare the vascular dementia rat model of chronic persistent ischemic. Observe the behavioral changes of VD rats, the Morphological changes of tissues in the hippocampus CA1 region, the expressional changes of neurons apoptosis in hippocampus CA1 region and nuclear factor-Kappa B(NF-κB), cyclooxygenase 2(cox 2),and the effects of donepezil on those changes. Discuss the possible mechanism of protecting the vascular dementia rats brain by the donepezil.Methods1,118 male SD rats weighing 250±30g, which were divided into sham operation group,model group and donepezil treatment group randomly, and further divided each group into January and February two sub-groups.2,Permanent bilateral common carotid arteries occlusion was used to prepare the vascular dementia rats model of chronic persistent ischemic.3,The drug treatment group was gavaged by 1mg/kg/d donepezil the second day after successfully modeling, the sham operation group and model group were gavaged by equal normal saline.4,Adopt Morris water maze to evaluate the behavior changes of each group rats in different times. Observe the morphological changes of neuronal cells of hippocampus CA1 area of each group rat in different times through HE staining. Adopt immunohistochemical staining to check the neuronal apoptosis of hippocampus CA1 area and the expression of NF-κB, COX-2 in different times.5,Compare the morphological changes of neuronal apoptosis, the expressions of NF-κB,COX-2 and the results of neuronal apoptosis of rats in each group at the same time point and the rats in the same group at different time points.6,All the data obtained were arranged by the EXCEL database and then analyzed with t-test or variance analysis by SPSS 13.0 statistics software. The analyzed result was expressed as mean±SD(x±s).Results1,The grade of Morris water maze showed:the time of avoiding incubation period of the model group and the medication treatment group is comparatively longer than the sham operation group in different time(one month and two month aft-er surgery). The time of avoid incubation period in medication group is obviously shorter than model group (P<0.01). The grade of one month model group is better than two month one in the comparison of sub-groups(P<0.05).2,The pathology finding:①The staining of HE shows that the rat pyramidal cells in hippocampus area of CA1 will become pycnosis, denaturalization, putrescent, losing, and grow severer as time pass by. The nerve cell will become further pycnosis and losing more severely. Pyramidal cells will become thinner, base material will become losen and create the micro-vacuole. On the other hand, the rat pyramidal cells in treatment group become lighten obviously.②We used Immunohistochemistry staining method to observe synchronously, the number of positive cells of NF-KBp65 and COX-2 in model group is much higher than fake operation group (P<0.01). After the Donepezil treatment, the number of positive cell of NF-KBp65 and COX-2 is much less than model group (P<0.01)③The result of TUNEL staining shows that the hippocampus CAl area has neuron apoptosis of rat after operation, and as time gose by, CAl area neuronal apoptosis of rat in model group has further increased (P< 0.05), but the number of neuronal apoptosis of rat in treatment group is obviously lower than model group (P<0.01) Conclusions1,The expression of NF-KB andCOX-2 was significantly enhanced in the hippocampus CA1 area of rats with vascular dementia,inflammatory reaction.2,The expression of neuron apoptosis was significantly increased in the hippocampus CA1 area of rats with vascular dementia.3,Donepezil can play a protective role by inhibit the expression of neuron apoptosis,NF-KB and COX-2 in the brain.