铝诱导阿尔茨海默病模型大鼠的发病机制的实验研究

Experiment study on the pathogenesis of AD model rats induced by aluminum

目的探讨铝诱导的阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠的发病机制。方法选择健康3月龄SD大鼠48只,随机分为对照组、模型组(分为低、中、高剂量铝饲料组),每组各12只。模型组在常规饲料中添加不同剂量A1C13.6H2O喂饲大鼠,持续染毒3个月,制做AD动物模型。实验结束后,麻醉大鼠、打开胸腔、右心室采血、分离血清保存、快速取大脑,分离海马并取一部分用以测定海马中AchE、ChAT的活性以及Ach含量,其余海马和其它脑组织称重并做脑匀浆,检测脑组织及血清SOD活性和MDA水平。结果中、高剂量铝饲料组大鼠海马中AchE的活性明显高于对照组(P<0.01),ChAT活性明显低于对照组(P<0.01),Ach含量亦显著减少(P<0.01);与对照组比较,中、高剂量铝饲料组大鼠脑组织及血清中SOD活性均明显降低(P<0.01),MDA含量显著增高(P<0.01)。结论铝的过多摄入使大鼠处于胆碱能系统失衡和氧化应激(oxidative stress,OS)状态,二者协同作用可能是AD发病的重要因素。

Objective To observe the activities of acetylcholine sterase（AchE）and choline acetyltransferase（ChAT）in hippocampal tissues in the Alzheimer＇s disease（AD）model rats induced by aluminum and the content change of acetylcholine（Ach）,and to determine the SOD activities and the content change of MDA in brain tissues and serum in order to detect the pathogenesis of AD.Methods 48 healthy SD ratsof 3 months old were chose and randomly divided them into Control Group,Model Group（including low-dosed Al feed group,middle-dosed Al feed group and high-dosed Al feed group）.There were 12 rats in each group.The rats in model groups were fed with conventional feed mixed with A1C13·6H2O and exposed to that feeding for 3 months continuously to make AD animal model.After the experiment,rats were anesthetized,serum samples were collected and preserved.Their brains were quickly taken and separated for hippocampus.The activities of AchE and ChaT and the content of Ach in hippocampal tissues were determined.The rest of hippocampus and the brain tissues were made into brain homogenate.The SOD activities and MDA content in brain tissue and serum were determined.Results The activities of AchE in hippocampus in middle-and high-dosed Al feed groups were strikingly higher than those of Control Group（P〈0.01）.The activities of ChaT were strikingly lower than those of Control Group（P〈0.01）.The content of Ach also strikingly decreased（P〈0.01）.The SOD activities in brain tissues and serum of the rate in middle-and high-dosed Al feed group strikingly decreased compared with those of Control Group（P〈0.01）.The content of MDA strikingly increased too（P〈0.01）.Conclusion The excessive intake of Al makes the rats＇ cholinergic system unbalanced and the rats are in the state of oxidative stress（OS）.The synergy of both the unbalanced cholinergic system and OS may be the important elements of AD.