【作者】 韩丽英；

【导师】 田心；

【作者基本信息】 天津医科大学 ， 生物医学工程， 2004， 硕士

【摘要】 目的 Aβ脑内沉积对神经组织具有毒性作用而导致痴呆，是目前较被公认的AD发病机制假说之一。基于这一假说，通过Aβ脑内注射以探讨制备AD大鼠模型的可行方法及其有效性，并通过Morris水迷宫行为学测试和认知区脑电频谱特性的AD特征检测，对所制备的AD大鼠模型进行评估和认定。 方法 本论文以老年性痴呆(AD)大鼠为研究对象，采用Aβ在大鼠海马CA1区微量注射方法制备AD大鼠模型。并分别对模型组和正常组大鼠应用Morris水迷宫行为学测试，包括5天10个时段定位航行实验，和撤去平台的空间探索实验。以正常大鼠的平均运动时间为基准，模型大鼠的平均运动时间延长20％为轻度痴呆，20％-30％之间为中度痴呆，40％以上为重度痴呆。从模型组大鼠中分别筛选出符合上述条件的不同痴呆程度的AD大鼠。对正常和AD大鼠在额叶皮层、枕叶皮层和海马(颞区)等认知相关脑区的自发脑电进行功率谱分析，以研究AD大鼠的脑电频率特性。 结果 1．Morris水迷宫行为学测试实验的主要结果是： (1)定位航行实验结果：模型组大鼠的运动时间较对照组的明显延长，运动距离较对照组的明显增长、平台象限记忆频度比正常大鼠的明显偏低、4环内搜索点数和记忆得分低于对照组； (2)空间探索实验结果：模型组大鼠运动距离比对照组大鼠的明显延长，平台象限的时间分布比对照组大鼠的明显要少，模型组大鼠对平台的搜索范围较广，不能集中在平台为圆心的4环内。 中文摘要 2.按照筛选标准，从制备的AD模型大鼠中筛选出4只符合痴呆标准的AD大鼠:6号为中度痴呆，l号、2号和5号为轻度痴呆。痴呆率，即AD大鼠的制备成功率为57.1%。 3.AD和正常大鼠认知脑区脑电频谱分析结果: AD模型大鼠脑电的a波功率降低，节律慢化:6波和e波功率明显增高。结论 1.本研究中AD大鼠的制备成功率达57.1%，证实了A已脑内注射方法是制备AD大鼠模型有效可行的方法，支持了A日脑内沉积造成神经系统损害导致痴呆的假说。 2.MorriS水迷宫行为学测试的定位航行实验和空间探索实验结果表 明:(1)应用行为学指标(运动时间)可以作为筛选AD大鼠的指标; (2)AD大鼠的学习能力和记忆能力都比正常对照组有明显降低。 3.本研究中对AD大鼠认知脑区自发脑电的频谱特征分析结果呈现了AD脑电特征:。波节律慢化，功率下降(或消失);慢波(6波和0波)活动增加，功率增高。更多还原

【Abstract】 Objective: The aim of this thesis is to research the theory and feasible method for Alzheimer’ s disease(AD) with rat model by microinjecting AB into cerebrum, to explore the ability of learning and space memory of AD rats by performing Morris water maze behavior examination, and to analyse the AD electroencephalography(EEG) frequency characters via frequency analysis of EEG in the brain area related with cognitive areas of rats. The AD rat is successfully modeled and verified by behavior examination and EEG frequency characters analysis at cerebral areas related with cognitive function in rats brain. Methods: To model the Alzheimer’ s disease for rat, the AB was microinjected into hippocampal CA1 area. Two weeks later, Morris water maze behavior examination was performed, which included 5-day place navigation with a fixed platform randomly placed in one quandrant, and spatial probe test without platform. The related data, such as movement time, movement distance, and the memory percentage for the platform quandrant etc, was recorded. Respectively compared with the average of the normal rats’ movement time, 4 of the 7 modeled rats with different dementia degree were chosen from the madeled rats, with 1 mild and 3 medium dementia. The EEG in the brain areas related with cognitive function (frontal lobes, occipital lobes and temporal area) were recorded in both normal and AD rats, to analyse the power spectrum and to study the AD EEG frequency feature of the AD model rats.Results:1. 7 rats in model group were microinjecte AB into the cerebrum. Based on the dementia chosen criteria, 1 of 7 model rats was the moderate dementia and 3 of 7 were mild dementia. The success rate of the AD rats is 57. 1% in this research.2. The main results of Morris water maze behavior examination are as follows:(1)place navigation: The movement time of the AD rats is markedly more than that of normal, the movenment distance of the AD rats is highly longer than that of normal, and the platform memory percentage of the AD rats is much lower than that of normal. The search points and the memory mark are also less than normal.(2)Spatial probe test: The movement distance in AD rats is obviously longer than that of normal, its time percentage of the original platform quandrant is low compare with the normal.3. The EEG frequency feature in the cerebral cognitive areas in two groups are as follows:The a -band power of EEG decreased in AD rats, with slower frequency. The power of the -band and the -band increased significantly. Conclusions:1. In the study the success rate of making AD model is 57.1%, showing that the microinjection of AB into rat cerebrum is an effect and feasible method for modeling the AD rats. This results supported the hypothesis in some degree that the AB deposition would lead to theneural system damaged as well as dementia.2. The results of Morris water maze behavior examination shown that the movement time could be used as a choosing criteria for AD rats, and that the learning and memory of the AD rats decreased notably compared with the normal rats.3. With the analysis of the frequency features of the EEG in brain areas, which is related to cognitive function, of AD rats, EEG features could be seen as such: the rhythm of the a wave were slowed down, its power decreased or even disappeared. Activaties of the slow waves( band and band) increased, with the power raised.更多还原