β淀粉样蛋白1～42与D-半乳糖联合作用建立复合阿尔茨海默病样模型  

By D-galactose injection combined with Aβ_(1-42) to establish a multiple animal model for Alzheimer's disease

作　　者：汪润[1] 赵丽娟[1] 王全英[1] 秦婷[1] 孙茂民[1] 夏春林[1] 

机构地区：[1]苏州大学医学部解剖学教研室暨细胞神经生物学研究室,江苏苏州215213

出　　处：《解剖学报》2011年第4期461-464,共4页Acta Anatomica Sinica

摘　　要：目的探讨β淀粉样蛋白1～42(Aβ1-42)及D-半乳糖(D-gal)联合应用构建复合阿尔茨海默病(AD)样模型的可行性。方法采用44只2月龄雄性SD大鼠,共分4组,即腹腔及侧脑室注射生理盐水的假手术组,腹腔注射D-gal或侧脑室注射Aβ1-42分别建立的D-gal组和Aβ1-42组,腹腔注射D-gal联合侧脑室注射Aβ1-42建立的复合AD模型组。Morris水迷宫实验检测大鼠的学习记忆能力,尼氏染色观察神经元数量和形态变化,生物化学方法检测血浆及脑组织匀浆中总抗氧化能力(T-AOC),免疫组织化学方法检测晚期糖基化终产物受体(AGER)在脑组织中的表达。结果与假手术组、Aβ1-42组、D-gal组相比,复合模型组大鼠水迷宫实验的潜伏期延长,认知记忆能力下降;海马和大脑皮质中神经元数量减少,可见胞体缩小、胞膜皱缩、胞核固缩浓染的细胞;血浆和脑组织匀浆中T-AOC下降;大脑皮质、海马、小脑皮质和小脑核AGER阳性表达细胞增多,呈棕褐色深染。结论在应用D-gal建立记忆缺失模型的基础上,联合注射Aβ1-42可建立复合AD样模型,较全面地模拟AD行为学、组织学及生物化学特征。Objective To establish a multiple Alzheimer＇s disease （AD） animal model by β Amyloid protein 1-42 （Aβ1-42） combined with D-galaetose （D-gal） injection. Methods Forty-four 2 months-old SD male rats were divided randomly to 4 group： peritoneal and lateral ventricle injection of physiological saline served as sham group; peritoneal injection of D-gal or lateral ventricle injection of Aβ1-42 individually served as a single factor AD model; peritoneal injection of D-gal combined with lateral ventricle injection of Aβ1-42 established a multiple AD animal model. Morris water maze test the learning and memory capacities. The changes of neuron number and morphology were detected by toluidine blue staining. The activity of the total antioxidant capacity （T-AOC） in serum and brain tissue homogenate were determined by spectrophotometry. The expression of aged-associated protein receptor （AGER） was detected by immunohistochemistry. Results Comparing with the sham group, Aβ1-42 group and D-gal group, the multiple model group exhibited a prolonged latency period which means a higher degree of cognitive and memory impairment; the neurons of hippocampus and cerebral cortex in multiple model group were reduced significantly and plasmalemma shrink, karyopyknosis and trachychromatic neurons increased; the T-AOC of serum and brain tissue in multiple model group declined obviously; the expression of AGER in cerebral cortex, hippocampus, cerebellar nuclei and cerebellar cortex of the multiple model group increased significantly and the staining of the AGER positive cells was traehychromatic and showed dark brown. Conclusion Injection of Aβ1-42 on D-gal induced neuronal cell death and memory impairment can serve as an ideal AD model more capable of mimicking behavioral, pathological and neurochemieal alterations in AD patient.

关 键 词：Β淀粉样蛋白 D-半乳糖 阿尔茨海默病 动物模型 学习记忆 免疫组织化学 大鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学]