阿尔茨海默病动物模型制备方法的研究

发布时间：2018-06-21 12:26

本文选题：阿尔茨海默病 + 动物模型　；参考：《新疆医科大学》2005年硕士论文

【摘要】：目的:探讨以AlCl_3鞘内注射法建立阿尔茨海默病动物模型的可行性以及与腹腔注射AlCl_3、D-半乳糖造模方法的比较,并对应用此两种方法建立阿尔茨海默病(AD)的动物模型进行初步评价。方法:12个月龄SD大鼠,分三个实验。分别予AlCl_3鞘内注射5d的方法,确定理想的给药浓度;确定理想的生物材料采集时间;以理想的给药浓度及生物材料采集时间重复实验,建立AD鞘内注射模型。同时以12个月龄SD大鼠腹腔注射AlCl_3、D-半乳糖建立AD腹腔注射动物模型。实验均在行为学实验结束后取脑,常规石蜡切片,SABC法进行β-AP、β-APP和tau免疫组织化学染色,观察β-AP、β-APP、tau阳性细胞表达。β-AP免疫组化染色观察SP形成,HE染色观察GVD变化,海马皮层神经元细胞计数。Bielschowsky染色观察NFTs。结果:鞘内注射模型:实验一、二:确定理想的鞘内注射浓度1.5%,生物材料采集时间33天。实验三:重复造模成功。行为学试验模型组比对照组错误次数明显增加,潜伏期明显缩短。模型组皮质、海马β-AP、tau、β-APP免疫阳性神经细胞数量明显增多,表达量增强。模型组顶叶锥体层锥体细胞、海马锥体细胞数显著减少。各组海马神经细胞均发生GVD,模型组GVD细胞数有明显增加;模型组可见神经纤维缠结样病理改变和β-AP沉积。腹腔注射模型:行为学结果模型组比对照组错误次数明显增加,潜伏期明显缩短。可见模型组皮质和海马神经细胞损伤、丢失。GVD细胞数有明显增加,β-AP、tau、β-APP表达的增强、海马及皮层β-AP沉积明显增加,未出现NFT和SP。结论:AlCl_3、D-半乳糖腹腔注射模型虽然在行为学及特征蛋白表达方面与AD有相似
[Abstract]:Objective: to explore the feasibility of establishing animal model of Alzheimer's disease by intrathecal injection of AlCl3 and to compare it with AlCl3D- galactose, and to evaluate the animal model of Alzheimer's disease (AD) by using these two methods. Methods: SD rats aged 12 months were divided into three groups. The method of intrathecal injection of AlCl3 for 5 days was used to determine the ideal drug concentration, to determine the ideal collection time of biomaterials, and to establish the intrathecal injection model of AD by repeated experiments with ideal administration concentration and collection time of biomaterials. At the same time, AD model was established by intraperitoneal injection of ALCL _ 3 and D-galactose into SD rats of 12 months old. The brain was taken from the brain after the behavioral experiment, and the 尾 -APP, 尾 -APP and tau immunohistochemical staining were performed by routine paraffin section with SABC method. The expression of 尾 -AP, 尾 -APP tau positive cells was observed. The SP formation and HE staining were observed by immunohistochemical staining, and the changes of GVD were observed by using 尾 -AP immunohistochemical staining. The number of neurons in hippocampal cortex was observed by Bielschowsky staining. Results: intrathecal injection model: experiment 1 and 2: determine the ideal intrathecal injection concentration 1.5 and biomaterial acquisition time 33 days. Experiment three: repeated modeling success. The number of errors and latency of behavioral test model group were significantly increased than that of control group. In the model group, the number of 尾 -APP immunoreactive neurons and the expression of 尾 -APP immunoreactive neurons in hippocampus were significantly increased. In the model group, the number of pyramidal cells and hippocampal pyramidal cells in the parietal pyramidal layer decreased significantly. GVD was found in hippocampal neurons in all groups, and the number of GVD cells in model group was significantly increased, and neurofibrillary tangle like pathological changes and 尾 -AP deposition were observed in model group. Intraperitoneal injection model: behavioral results showed that the number of errors in the model group was significantly higher than that in the control group, and the incubation period was significantly shortened. In the model group, the number of lost .GVD cells increased, the expression of 尾 -APtauand 尾 -APP increased, the deposition of 尾 -AP in hippocampus and cortex increased, and no NFT or SPP appeared. Conclusion though the behavior and characteristic protein expression are similar to those of AD in the behavior and characteristic protein expression of the mice injected with Dgalactose into the abdominal cavity of the mice with 10% AlCl3, it is similar to AD.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R-332

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