摘要
目的:根据正交试验原理,应用3种化学物质诱发大鼠认知障碍模型,判定模型质量,试图优化出建立阿尔茨海默病(AD)模型的方法。方法:健康雌性Wistar大鼠16只,按L16(215)正交试验设计分组观察,依二水平三因素的方法制备模型。三因素为:A因素:一水平为鹅膏蕈氨酸(IBA)一次性微量(1μL,120mmol/L)注入大鼠Meynert基底核;二水平为注射等量人工脑脊液。B因素:一水平为β淀粉样肽1～40(Aβ1～40,20μL)左侧脑室注射,1次/d,连续1周;二水平注射等量人工脑脊液。C因素:一水平为D-半乳糖(D-gal,48mg/kg)皮下注射,1次/d,连用56d;二水平注射等量生理盐水。在处理前后用MG-2迷宫观察大鼠学习记忆成绩。苏木精-伊红染色观察神经细胞形态和数量,Bielschowsky染色观察神经元纤维缠结(NFT)和老年斑等病理改变。结果:应用三因素150d后,IBA,Aβ1～40,D-gal联合应用可致大鼠记忆障碍(均方:7.5625;F=8.067;P<0.05);海马皮层锥体细胞数量明显减少(P<0.01),Alzheimer细胞增多及卫星现象。IBA致大鼠学习记忆障碍(均方:915.0625,10.5625,F=10.602,11.267;P<0.05,0.05);D-gal致大鼠学习障碍(均方:495.0625,F=5.736;P<0.05)。3种化学物质及其交互效用分别可致海马皮质锥体细胞数量明显减少(1.4±0.28,2.2±0.85,1.7±0.14,1.8±0,0.
AIM:To induce the rat models of cognitive disorder by using 3 chemicals according to the orthogonal experimental design,so as to optimize the methods of establishing the models of Alzheimer disease(AD). METHODS:Totally 16 healthy male Wistar rats were observed in groups according to the orthogonal experimental design and the models were established by injection of chemicals according to 2 levels and 3 elements. The element A: one level is Ibotenic acid(IBA;1 μL,120 mmol/L) that was injected into the Meynert nucleus by using microdrive injector;Element B: one level is β-amyloid peptide 1-40(Aβ1-40,20 μL) that was injected into the left lateral ventricle,once a day for a week continuously;Element C:one level was D-galactose(D-gal,48 mg/kg) that was used by subcutaneous injection,once a day for 56 days successively.The another level was the same methods but using the artificial cerebrospinal fluid(CSF) or normal saline instead of IBA,Aβ1-40 or D-gal.The abilities of learning and memory were tested with the MG-2 maze.The pathological changes of brain,such as neurofibrillary tangle(NFT) and senile plaque(SP),were observed by using HE staining and Bielschowsky staining. RESULTS:After 150 days,the application of IBA,Aβ1-40 and D-gal three elements together could cause cognitive disorders of rats in memory(7.562 5, F=8.067,P< 0.05),the amounts of pyramidale were obviously decreased in cortex of hippocampus(P< 0.01),increase of Alzheimer cells and satellitism were also observed.IBA could cause cognition disorders of rats in learning and memory(915.062 5,10.562 5,F=10.602,11.267;P< 0.05,0.05);D-gal could cause cognition disorders of rats in memory(495.062 5,F=5.736;P< 0.05);Every chemical and their interactive effects could decrease the amounts of pyramidale in cortex of hippocampus(1.4±0.28,2.2±0.85,1.7±0.14,1.8±0,0.8±0.85,1.3±0.99,2.2±0.85,1.5±1.27,1.7±0.14)(P< 0.01).No NFT and SP were observed. CONCLUSION:IBA and D-gal can result in cognitive disorder and pathological changes of hippocampus respectively,but the application of the three chemicals together has better effect.
出处
《中国临床康复》
CSCD
2004年第25期5266-5268,共3页
Chinese Journal of Clinical Rehabilitation
基金
青岛市科技局基金资助项目(SG9702-403)
山东省科技厅基金资助项目(003130110)~~
