实验性阿尔茨海默病大鼠模型行为学、神经生化学及病理学特征

Praxiological,neurobiochemical and pathological characteristics of experimental animal model of Alzheimer's disease

目的:建立符合阿尔茨海默病(Alzheimer'sdisease,AD)行为学、神经生化学及病理学特征的实验性AD动物模型。方法:采用β-淀粉样蛋白(Aβ)大鼠侧脑室注射联用转移生长因子β1(tiansforminggrowfkfactorβ1,TGFβ1)脑内注射改良并制作实验性AD大鼠模型。应用避暗法和水迷路法测定AD模型大鼠学习记忆功能,免疫组化及图像分析定量法检测模型大鼠大脑皮质和海马结构CA1区Aβ沉积斑数目及截面积。同时还应用放射免疫法测定大鼠皮质和海马乙酰胆碱含量、胆碱乙酰化酶(ChAT)和乙酰胆碱酯酶(AchE)活性。结果:经改良由Aβ联用TGFβ1诱导的实验性AD模型大鼠既表现有行为学改变(学习记忆障碍),又具典型的AD病理学特征(Aβ沉积斑),模型组Aβ沉积斑数目和截面积大脑皮质为(32.5±6.7)个/mm2,(1904.3±86.3)μm2,CA1区为(11.4±5.3)个/mm2,(1466.3±98.4)μm2。同时还出现与AD相一致的神经生化(神经递质)改变。结论:Aβ联用TGFβ1诱导的实验性AD大鼠模型是一接近临床的较好模型,可用于抗痴呆药物的筛选和药效评价。

AIM:To establish experimental animal models in accord with the praxiological,neurobiochemical and pathological characteristics of Alzheimer’s disease(AD).METHODS:Beta amyloid protein(Aβ) injection into lateral ventricle in rats and transforming growth factor beta1(TGF β1) injection into the rat's brain tissue were applied to make experimental rat model of AD. Step through test and water maze test were employed to investigate ability of learning and memory in AD model rats,immumohistochemical method and image pattern analysis quantitative method were used to detect the deposition number and cross area of Aβin cerebral cortex and hippocampus CA1 in experimental AD model rats.In addition,radioimmunoassay was applied to measure content of acetylcholine,activity of choilne acetylase(ChAT) and cholinesterase(AchE) of cerebral cortex and hippocampus.RESULTS:Through improving, there were changes of behaviour(impairment of learning and memory) as well as typical AD pathological features(Aβdeposition plaques) in AD model induced by Aβand TGF β1.The deposition number and cross area of Aβwere(32.5±6.7)/mm2 and(1 904.3±86.3) μm2 in the cortex and(11.4±5.3)/mm2 and (1 466.3±98.4) μm2 in the hippocampus CA1 in model group respectively.In the meanwhile, neurobiochemical changes(neurotransmitter) were identical with AD. CONCLUSION:Experimental AD rat model induced by Aβand TGF β1 is a comparatively perfect clinical model, which can be used to screen the anti dementia drugs and evaluate drug effect.