本文選題：阿爾茨海默病 + 動(dòng)物模型　； 參考：《新疆醫(yī)科大學(xué)》2005年碩士論文

【摘要】：目的:探討以AlCl_3鞘內(nèi)注射法建立阿爾茨海默病動(dòng)物模型的可行性以及與腹腔注射AlCl_3、D-半乳糖造模方法的比較,并對(duì)應(yīng)用此兩種方法建立阿爾茨海默病(AD)的動(dòng)物模型進(jìn)行初步評(píng)價(jià)。方法:12個(gè)月齡SD大鼠,分三個(gè)實(shí)驗(yàn)。分別予AlCl_3鞘內(nèi)注射5d的方法,確定理想的給藥濃度;確定理想的生物材料采集時(shí)間;以理想的給藥濃度及生物材料采集時(shí)間重復(fù)實(shí)驗(yàn),建立AD鞘內(nèi)注射模型。同時(shí)以12個(gè)月齡SD大鼠腹腔注射AlCl_3、D-半乳糖建立AD腹腔注射動(dòng)物模型。實(shí)驗(yàn)均在行為學(xué)實(shí)驗(yàn)結(jié)束后取腦,常規(guī)石蠟切片,SABC法進(jìn)行β-AP、β-APP和tau免疫組織化學(xué)染色,觀(guān)察β-AP、β-APP、tau陽(yáng)性細(xì)胞表達(dá)。β-AP免疫組化染色觀(guān)察SP形成,HE染色觀(guān)察GVD變化,海馬皮層神經(jīng)元細(xì)胞計(jì)數(shù)。Bielschowsky染色觀(guān)察NFTs。結(jié)果:鞘內(nèi)注射模型:實(shí)驗(yàn)一、二:確定理想的鞘內(nèi)注射濃度1.5%,生物材料采集時(shí)間33天。實(shí)驗(yàn)三:重復(fù)造模成功。行為學(xué)試驗(yàn)?zāi)Ｐ徒M比對(duì)照組錯(cuò)誤次數(shù)明顯增加,潛伏期明顯縮短。模型組皮質(zhì)、海馬β-AP、tau、β-APP免疫陽(yáng)性神經(jīng)細(xì)胞數(shù)量明顯增多,表達(dá)量增強(qiáng)。模型組頂葉錐體層錐體細(xì)胞、海馬錐體細(xì)胞數(shù)顯著減少。各組海馬神經(jīng)細(xì)胞均發(fā)生GVD,模型組GVD細(xì)胞數(shù)有明顯增加;模型組可見(jiàn)神經(jīng)纖維纏結(jié)樣病理改變和β-AP沉積。腹腔注射模型:行為學(xué)結(jié)果模型組比對(duì)照組錯(cuò)誤次數(shù)明顯增加,潛伏期明顯縮短�？梢�(jiàn)模型組皮質(zhì)和海馬神經(jīng)細(xì)胞損傷、丟失。GVD細(xì)胞數(shù)有明顯增加,β-AP、tau、β-APP表達(dá)的增強(qiáng)、海馬及皮層β-AP沉積明顯增加,未出現(xiàn)NFT和SP。結(jié)論:AlCl_3、D-半乳糖腹腔注射模型雖然在行為學(xué)及特征蛋白表達(dá)方面與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.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類(lèi)號(hào)】：R-332

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