Experimental Study On The Effect Of Donepezil On Nerve Cell Of Rat Brain, Learning And Memory Of Vascular Dementia Model Rat

Objective: To replicate the global cerebral ischemia-reperfusion injury induced vascular dementia model in rats, after Donepezil was given, the spatical learning and memory of rats was measured, meanwhile, glial fibrillary acidic protein(GFAP) and intercellurer adhesion molecule-1(ICAM-1) expression was measured, and in the end, to investigate the cerebral protective role of Donepezil and the probally mechanism.Methods: 60 male SD rats, weighing 250～280g, were randomly divided into 1: sham operation group, 2: ischemia-reperfusion injury model group, 3: medication group, each group had 20 rats. According to wangrui, the imitative vascular dementia model was established by repeatedly clipping the common carotid artery and reducing blood pressure with an abdominal injection of sodium nitroprusside. Donepezil was given to the rat in medication group every day. The spatical learning and memory of rats following injury was measured at 10d, 11d, 12d, and 13d by means of Y-maze. At 14d, the rats were killed, which were fixed through anteriothora and then the removed brain was fixed in 0.1M PBS of 4% paraformaldehyde at 4℃for 24h. After regular dehydrating and embedding in paraffin, the brain was sectioned serially coronoidly, 5μm thickness. The tissue section followed by washing in xylen to dewax and rehydration through a faded series of ethanal and redist water. After that, HE staining, immunohistochemical staining with GFAP, ICAM-1,Bcl-2 and Bax were performed, and immunohistochemical positive cell immunoreactivity was detected byBioSens digital imaging analysis system. The obtained data were expressed as x±s.Results:In model group, the error number was increased and the total reaction time was increased significantly compared with in sham operation group in Y-maze experiment (p<0.01). As to in medication group, they were decreased significantly compared with in model group(p<0.01).HE staining showed slightly loosened brain tissue and cells edema in medication group, the structure of brain tissue is close to that of the sham operation group. In model group, the structure of brain tissue changed so much that it could hardly be identified, a large number of deep-dyeing neurons, scattered degenerated and necrotic neuron were observed, nucleuses were condensed.Corresponding sham operation group, lots of GFAP and ICAM-1 positive cells could be seen in model group, less likely to be seen in medication group than in model group (p<0.01).Bcl-2 and Bax positive cell could be seen occasionally in sham-operation group. Bcl-2 immunoreactivity in model group increased a little compareng with that in medication group, but Bax positive cell in medication group increased more obviously compareng with that in medication group (p<0.01).Conclusion:①DP decreases the expression of GFAP and ICAM-1 of vascular dementia model rat to inhibiting cortical and hippocampal neurons injury by the global cerebral ischemia-reperfusion.②DP increases the expression of Bcl-2 and decrease the expression of Bax to inhibiting the apoptosis of cortical and hippocampal neurons, then protect the function of the cerebral.