摘要
目的:通过双侧丘脑注射β-淀粉样肽42(amyloidβ-peptides 42,Aβ_(42))寡聚体构建阿尔茨海默病(Alzheimer disease,AD)小鼠动物模型。方法:将120只雄性C57BL/6小鼠随机分为假手术组、溶剂组和Aβ组,每组40只。Aβ组利用立体定位技术将Aβ_(42)寡聚体注射至双侧丘脑。术后3、7、14和28 d分别利用Morris水迷宫实验评价动物神经功能;免疫组化和Western blot检测小鼠双侧丘脑神经元核抗原(neuronal nuclear antigen,NeuN)、胶质细胞原纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、离子钙结合适配器分子1(ionized calcium binding adapter molecule 1,Iba1)和磷酸化tau蛋白[p-tau(Ser396)]水平。结果:与假手术组和溶剂组相比,Aβ组小鼠平均逃避潜伏期显著延长,穿越原平台次数和在原平台所在象限游泳时间显著减少(P<0.05),Aβ组小鼠GFAP、Iba1和p-tau(Ser396)水平显著升高,而NeuN表达显著减少(P<0.05)。结论:Aβ_(42)寡聚体小鼠双侧丘脑注射法是构建AD动物模型的新方法。
AIM:To establish a mouse model of Alzheimer disease(AD)by injecting amyloidβ-peptide 42(Aβ_(42))oligomers into the bilateral thalamus.METHODS:Male C57BL/6 mice were randomly divided into sham group,vehicle group and Aβgroup with 40 mice in each group.The Aβ_(42) oligomers were injected into bilateral thalamus by a ste‐reotaxic technique in Aβgroup.At 3,7,14 and 28 d after the operation,neurological function was tested by the Morris water maze experiment.Immunohistochemistry and Western blot were used to detect the protein levels of neuronal nuclear antigen(NeuN),glial fibrillary acidic protein(GFAP),ionized calcium binding adapter molecule 1(Iba1)and p-tau(Ser396)in the thalamus.RESULTS:Compared with sham group and vehicle group,the average escape latency was sig‐nificantly longer,the times of crossing the original platform and the time of swimming in the quadrant were significantly re‐duced in the Aβgroup(P<0.05),and the levels of GFAP,Iba1 and p-tau(Ser396)in Aβgroup were significantly in‐creased,but the expression of NeuN was significantly decreased(P<0.05).CONCLUSION:Injection of Aβ_(42) oligomers into bilateral thalamus might be a new method to establish AD animal model.
作者
丁燕
朱培植
宋萍萍
刘昱君
张玉生
DING Yan;ZHU Peizhi;SONG Pingping;LIU Yujun;ZHANG Yusheng(Department of Neurology,The First Affiliated Hospital of Jinan University,Guangzhou 510630,China;Department of Neurology,Dongguan Tungwah Hospital,Dongguan 523000,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2023年第6期1136-1144,共9页
Chinese Journal of Pathophysiology
基金
广东省自然科学基金资助项目(No.2020A1515011249)
广州市-暨南大学市校联合基金资助项目(No.2023A03J00442)
广东省潮州市卫生健康局科研项目(No.2021068,No.2022089)。
关键词
淀粉样肽
丘脑
阿尔茨海默病
小鼠模型
amyloidβ-peptides
thalamus
Alzheimer disease
mouse model
