动物造模,高胆固醇 z-bo 2020-09-08 371

　　Purpose: To observe the pathological changes of brain tissue in sporadic WHBE rabbit Alzheimer's disease (AD) model.

　　Methods: Thirty male WHBE rabbits were randomly divided into 3 groups: normal control (NC) group, high cholesterol diet (HCD) group, high cholesterol diet + copper drinking water (HCD + Cu 2 +) group, each with 10 rabbits; Take 10 old WHBE rabbits as the Senile group. The NC group and Senile group were given normal diet, the HCD group was given 2% cholesterol diet, and the HCD + Cu 2 + group was given 2% cholesterol diet and added 0.12 ppm copper drinking water, and the models were continuously made for 12 weeks. Twelve weeks after the model was built, blood was taken to measure the levels of total cholesterol (TC) and β-amyloid (Aβ) 1-42; a part of brain tissue was taken to measure the activity of superoxide dismutase (SOD) and malondialdehyde in the cortex and hippocampus (MDA) content, another coronal slice of brain tissue was subjected to immunohistochemical staining to observe the positive expression of Aβ, β-secretase 1 (BACE1), and phosphorylated tau (p-tau) protein. At the same time, the sections were sectioned with Congo red and Persu The conditions of senile plaques and neurofibrillary tangles were observed by Bielschowsky staining.

　　Results: The body weight of WHBE rabbits in the elderly group was significantly higher than that of the NC group (P<0.01), and the plasma TC and Aβ 1-42 of each group were significantly higher than those of the NC group (P <0.05, P <0.01); The SOD activity in the brain tissue of the group was significantly lower than that of the NC group (P <0.05), and the MDA content was significantly higher than that of the NC group (P <0.05, P <0.01). Immunohistochemical staining showed that the positive expressions of Aβ, BACE1, and p-tau protein in the brain tissues of each group were significantly higher than those in the NC group (P <0.05, P <0.01), and the brain tissue of the HCD + Cu 2 + group The positive expression of BACE1 and p-tau protein was also significantly higher than that in the HCD group (P<0.05, P<0.01). Congo red and Bielschowsky staining showed that a large number of senile plaques and neurofibrillary tangles were observed in the brain tissue of the WHBE rabbits in the HCD group, HCD + Cu 2 + group and the elderly group.

　　Conclusion: High-cholesterol diet or supplemented with trace copper drinking water can induce obvious AD pathological changes in the brain of sporadic AD model WHBE rabbits, including oxidative damage, increased Aβ deposition in the brain, senile plaques and tau pathology. WHBE rabbits can be used for Research on animal models of neurodegenerative diseases.