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Experimental Study on the Effect of Donepezil on Nerve Cell of Rat Brain, Learning and Memory of Vascular Dementia Model Rat

Author: ZuoYunFeng
Tutor: MaXingMing
School: Lanzhou University
Course: Medical Immunology
Keywords: Vascular Dementia Rats GFAP ICAM-1 Bcl-2 Bax Hydrochloride donepezil Learning and memory
CLC: R96
Type: Master's thesis
Year: 2007
Downloads: 78
Quote: 0
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Abstract


Objective: A rat model of global cerebral ischemia-reperfusion induced vascular dementia, DP reperfusion of ischemic rat spatial learning and memory function observed after application of DP intervention, detection of inflammation-related indicators in rat cortical to explore the application of DP on the possible mechanisms of the protective effect of cortical and hippocampal neurons and hippocampal expression. Methods: Male SD rats 60, weighing 250 to 280g, were randomly divided into three groups: sham operation group, model control group, DP treatment group (n = 20). In accordance with the the Rui method using intraperitoneal injection of sodium nitroprusside and repeated clipping of bilateral carotid artery, causing vascular dementia animal models. DP treatment group DP administered orally once a day. Rats' learning and memory function in the model after 10 days, 11 days, 12 days, 13 days, using a Y-shaped maze test. 14 days after surgery, the rats were sacrificed, after cardiac fixed, the brains were fixed for 24 hours in 4 ℃ downstream in 4% paraformaldehyde in 0.1M phosphate buffer, dehydrated, embedded in paraffin, coronal surface continuous slice thickness of about 5μm, water to xylene dewaxing and alcohol gradient. Biopsy specimens were stained the following: ① HE staining; ② GFAP, ICAM-1, Bcl-2 and Bax immunohistochemical staining using BioSens digital imaging image analysis system for quantitative analysis. The experimental data (?) ± s. Results: In the maze test of learning and memory performance of the model control group was significantly lower than the sham group and the DP treatment group showed throughout the day, an increase in the number of errors, reaction time (P <0.05), and then the results between the two groups had no significant difference. HE staining showed uniform cortical staining sham group, the number of nerve cells, tightly packed, uniform size, neat structure. The nuclei were round or oval, prominent nucleoli. Model control group loose brain tissue, swelling of nerve cells cell vacuolation was big, nucleus deformation karyopyknosis shows that a large number of deeply stained nerve cells, gliosis obvious. DP treatment group was significantly better than the model control group, showing uniform cortical staining, swelling of the nerve cells, large number, arranged in dense, neat structure. The nuclei were round or oval, nuclear slightly darkly stained nucleolus clear, slightly deformed. Seen a small amount of gliosis and a small amount of pyknotic degeneration of neurons. GFAP, ICAM-1 immunohistochemical expression: model control group cortex and hippocampus seen a large number of immunohistochemical positive cells DP treatment group, the number of positive cells between the model group and the sham group. The application of image analysis software the model control group GFAP, ICAM-1 expression was significantly enhanced significantly increased in the area and integrated optical density DP treatment group GFAP expression of ICAM-1 area and integrated optical density compared with the model control group was significantly reduce (P <0.01). Sham group Bcl-2 and Bax protein is only a small amount of expression. Model control group, Bcl-2 protein is highly expressed, but less (P <0.01) compared with the DP treatment group. Bax protein expression was decreased in the DP treatment group compared with the model control group (P <0.01). Conclusion: ① DP can reduce VaD rat model of GFAP, ICAM-1 overexpression alleviate neuronal damage, thereby improving the learning and memory abilities of rats with vascular dementia. ② DP can upregulate the antiapoptotic gene Bcl-2 expression level down the pro-apoptotic gene Bax expression levels, inhibition of apoptosis, thereby protecting neurons function.

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