中国实验动物学报2018，Vol.26Issue(3)：357-364,8.DOI:10.3969/j.issn.1005-4847.2018.03.014
高胆固醇饮食加铜水喂养WHBE兔引起的脑组织病理学改变
Brain histopathological changes in WHBE rabbits fed with high cholesterol diet plus copper drinking water
摘要
Abstract
Objective To observe the pathological changes of brain tissues in the WHBE rabbit model of sporadic Alzheimer disease (AD). Methods Thirty 3 -4-month old 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+ Cu2+) group, 10 in each group. Another 10 senile (36-48-month old) male WHBE rabbits were taken as senile group. The NC group and the senile group were fed a normal basic diet, the HCD group fed a 2% cholesterol diet, and the HCD+Cu2+group fed a 2% cholesterol diet plus 0. 12 PPM copper drinking water for 12 weeks. The levels of total cholesterol (TC) and β-amyloid protein (Aβ) 1-42 were measured at 12 weeks. The activity of superoxide dismutase ( SOD) and the content of malondialdehyde (MDA) in the cortex and the hippocampus were detected. In addition, the covered area of Aβ, β-site APP cleaving enzyme 1(BACE1) and phosphorylated tau (p-tau) protein in coronal sections of brain tissues were also observed by immunohistochemical staining. The senile plaques and the neurofibrillary tangles were observed by Congo red and Bielschowsky staining, respectively. Results The body weight of WHBE rabbits in the senile group was significantly higher than that of the NC group ( P ＜ 0. 01 ), and the plasma TC and Aβ1 -42 in each group were significantly higher than that in the NC group (P ＜ 0.05, P ＜ 0.01). The activity of SOD in brain tissues was significantly lower than that of NC group (P＜ 0. 05), and the MDA content was significantly higher than that of NC group (P＜ 0. 05, P ＜ 0. 01). Immunohistochemical staining showed that the covered area of Aβ, BACE1 and p-tau in brain tissues of all groups were significantly higher than that of NC group (P ＜ 0. 05, P ＜ 0. 01), and the covered area of BACE1 and p-tau protein in the brain tissues of HCD + Cu2+group was also significantly higher than that of the HCD group (P ＜ 0. 05, P ＜ 0. 01). Congo red and Bielschowsky staining showed that the number of senile plaques and neurofibrillary tangles were observed in the brain tissues of the HCD, HCD+Cu2+and senile groups. Conclusions High cholesterol diet or supplemented with trace copper drinking water can induce obvious AD pathological changes in WHBE rabbit models of sporadic AD with obvious oxidative damage, increased Aβ deposition and senile plaque in the brain, and pathological changes of tau. WHBE rabbit can be used in the study of animal models of neurodegenerative diseases.关键词
WHBE兔/散发性阿尔茨海默症/动物模型/β淀粉样蛋白/高胆固醇血症Key words
WHBE rabbit/sporadic Alzheimer's disease/animal models/β-amyloid protein/hypercholesterolemia分类
生物科学引用本文复制引用
徐剑钦,陈民利,刘军平,陈娇娇,陈诚,潘永明..高胆固醇饮食加铜水喂养WHBE兔引起的脑组织病理学改变[J].中国实验动物学报,2018,26(3):357-364,8.基金项目
浙江省科技厅公益性项目(No. 2016C37092) （No. 2016C37092）
浙江中医药大学比较医学创新团队(No. XTD201301) （No. XTD201301）
浙江省医药卫生科研基金项目(No. 2017KY123) （No. 2017KY123）
浙江省中医药科学研究基金(No. 2018ZA057).Funded by Public Projects of Zhejiang Province Science and Technology Department (No. 2016C37092) （No. 2018ZA057）
Zhejiang Chinese Medical University Comparative Medicine Innovation Team (No. XTD201301) （No. XTD201301）
Medical Science and Technology Project of Zhejiang Province (No. 2017KY123) （No. 2017KY123）
Traditional Chinese Medicine Scientific Research Funds of Zhejiang Province (No. 2018ZA057). （No. 2018ZA057）
