神经节苷脂1对β-淀粉样蛋白痴呆模型小鼠学习记忆障碍及大脑皮质相关生化指标的影响  

Effects of monosialotetrahexosyl ganglioside 1 on learning/memory deficiency and biochemical events of brain in amyloid β-protein-induced dementia mice

作　　者：董朝辉[1] 付爱玲[1] 黄世杰[1] 孙曼霁[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学与毒理学杂志》2006年第1期39-43,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的探索神经节苷脂1(GM1)是否有益于阿尔茨海默病的治疗。方法小鼠右脑室一次性注射β-淀粉样蛋白(β-AP)4nmol制作痴呆模型,d4起GM150mg·kg-1·d-1ip连续10d。水迷宫和暗箱实验测定小鼠学习记忆和空间辨别能力。测定小鼠大脑皮质胆碱乙酰转移酶(ChAT)和乙酰胆碱酯酶(AChE)活性,乙酰胆碱(ACh)、丙二醛(MDA)和谷胱甘肽(GSH)含量等生化指标。大脑组织切片观察病理学改变。结果GM1治疗组与痴呆模型组比较,被动回避实验中进入暗室时间延长,错误次数减少;水迷宫游泳时间缩短;大脑ChAT和AChE活性,以及ACh含量恢复正常;大脑皮质组织学病变改善;细胞凋亡减少。但对β-AP引起的大脑MDA的增多及GSH的减少无影响。结论GM1可明显改善β-AP所致痴呆模型小鼠空间学习记忆和辨别能力。但其作用并非通过抗氧化和清除自由基而实现。AIM To explore if monosialotetrahexosyl ganglioside 1 （ GM1 ） is beneficial to the therapy of Alzheimer＇s disease. METHODS Amyloid β-protein （β-AP） 4 nmol was icy injected once into the right lateral cerebral ventricle to establish the dementia model mice. From d 4, GM1 50 mg · kg· d^-1 was ip injected for 10 d. Learning/memory was examined by step through test and water maze test. The activities of choline acetyltransferase （CHAT） and acetylcholinesterase （AChE）, and the levels of acetylcholine （ACh）, malondialdehyde （MDA） and glutathione （GSH） were determined. The pathological changes in the cerebral cortex and hippocampus, and the influence of cell apoptosis were also investigated. RESULTS Compared with the dementia model mice, the retention time of the GM1-treated mice in step through test was lengthened, and the error number reduced; in water maze tests, the swimming time of GM1-treated mice was shortened. Furthermore, treatment of GM1 significantly reversed the elevated CHAT, AChE activities, and the decreased ACh content in the β-AP model mice. However, GM1 had no in- fluence on the increased MDA and decreased GSH levels. The pathological changes in the cerebral cortex and hippocampus were ameliorated a lot, and the cell apoptosis was reduced in GM1-treated mice. CONCLUSION The GM1 therapy obviously improves the learning/ memory and the special discrimination abilities of the β-AP-induced dementia model mice. It seems that the action of GM1 is not mediated by antioxidation and free radicals elimination.

关 键 词：神经节苷脂 阿尔茨海默病 淀粉样Β蛋白 学习 记忆 

分 类 号：R749.16[医药卫生—神经病学与精神病学]