动物造模 z-bio 2022-04-27 383

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

　　Methods: Thirty male WHBE rabbits were randomly divided into three groups: normal control (NC) group, high cholesterol diet (HCD) group, high cholesterol diet + copper drinking water (HCD + Cu 2 + ) group, 10 in each group; Ten elderly WHBE rabbits were selected as the elderly group. The NC group and Senile group were given normal feed, the HCD group was given 2% cholesterol feed, and the HCD + Cu 2 + group was given 2% cholesterol feed and 0.12 ppm copper drinking water, and the model was continuously established for 12 weeks. At the 12th week of modeling, blood was collected to measure the levels of total cholesterol (TC) and beta amyloid (Aβ) 1-42; some brain tissues were taken to measure the activity of superoxide dismutase (SOD) and malondialdehyde in cerebral cortex and hippocampus. (MDA) content, another coronal section of brain tissue was taken for immunohistochemical staining to observe the positive expression of Aβ, β-secretase 1 (BACE1) and phosphorylated tau (p-tau) protein. Bielschowsky staining was used to observe senile plaques and neurofibrillary tangles, respectively.

　　Results: The body weight of WHBE rabbits in the elderly group was significantly higher than that in the NC group ( P ＜ 0.01), and the plasma TC and Aβ1-42 in each group were significantly higher than those in the NC group ( P ＜ 0.05, P ＜ 0.01); The SOD activity in the brain tissue of the NC 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 brain tissue of each group were significantly higher than those of NC group (P ＜ 0.05, P ＜ 0.01), and HCD + Cu 2 + group brain tissue The positive expressions of BACE1 and p-tau protein were also significantly higher in the HCD group than 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 WHBE rabbits in HCD group, HCD + Cu 2 + group and aged group.

　　CONCLUSION: High cholesterol diet or combined addition of trace copper to 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 pathological changes. WHBE rabbits can be used for Studies in animal models of neurodegenerative diseases.