Lactacystin诱导黑质神经元变性死亡的帕金森病大鼠模型方法  

A rat model of Parkinson's disease by lactacystin-induced neuron degeneration in the substantia nigra

作　　者：段丽[1] 焦西英[1] 张磊[1] 夏毅[1] 丁银秀[1] 饶志仁[1] 陈良为[1] 

机构地区：[1]第四军医大学神经科学研究所,西安710032

出　　处：《神经解剖学杂志》2012年第2期109-113,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81071609);973项目(2011CB504103)

摘　　要：目的:探讨脑内定位注射蛋白酶体抑制剂Lactacystin诱导大鼠黑质神经元变性及运动症状的帕金森病大鼠模型方法。方法:成年雄性SD大鼠16只随机分为Lactacystin组和对照组,将Lactacystin 8μg(溶于0.8μl生理盐水)定位注入左侧内侧前脑束,对照组注射等量生理盐水。于1、3、5周时间点观察其运动行为,处死动物后进行中脑酪氨酸羟化酶和Fluoro-Jade C染色,显示分析黑质多巴胺神经元生存和变性死亡。结果:Lactacys-tin组黑质致密部酪氨酸羟化酶阳性神经元急剧减少,伴有大量Fluoro-Jade C阳性的变性神经元出现。Lactacystin组动物出现自发活动减少、运动缓慢、震颤和自发旋转,并呈逐渐加重的运动行为改变。结论:Lactacystin能够高效诱导黑质多巴胺神经元变性和运动障碍的大鼠模型,是研究帕金森病发病机制和神经保护的优良方法。Objective： To establish a rat model of Parkinson＇s disease by stereotaxical brain injection of lactacystin and inducement of nigral neuronal degeneration and motor disorder.Methods： Male adult SD rats（n=16） were randomly divided into lactacystin and control group.Lactacystin（8 μg dissolved in 0.8 μl saline） was stereotaxically injected into left medial forebrain bundle（MFB）,and same volume of saline was injected in control group.After open-field observation of spontaneous motor behaviors at 1 week,3 weeks and 5 weeks,all animals were sacrificed and nigral sections were processed for tyrosine hydroxylase（TH） and Fluoro-Jade C staining to visualize surviving dopaminergic neurons and degenerative neurons in the substantia nigra.Results：The TH-positive neurons were remarkably decreased,accompanied by appearance of numerous Fluoro-Jade C-positive degenerative neurons in lactacystin-lesioned side in the substantia nigra.The rats became progressive bradykinetic,tremor,rotation,and displayed spontaneous motor behavior changes after lactacystin injection.Conclusion： Lactacystin could effectively induce nigral dopaminergic degeneration and motor behavioral disorder,indicating that lactacystin rat model is suitable candidate for study of PD pathogenesis and neuroprotection.

关 键 词：帕金森病 Lactacystin模型 Fluoro-JadeC 多巴胺 神经变性 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]