蛋白酶体抑制剂诱导大鼠运动行为改变的研究  

Motor behavioral changes of rats induced by proteasome inhibitor

作　　者：潘琪[1,2] 牛朝诗[1,2] 程俊[1,2] 

机构地区：[1]安徽医科大学附属省立医院神经外科 [2]安徽省立体定向神经外科研究所,合肥230001

出　　处：《立体定向和功能性神经外科杂志》2007年第3期129-132,共4页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金：安徽省优秀青年科技基金项目(编号:04043072);安徽省人才开发基金项目(编号:2006Z037)

摘　　要：目的观察蛋白酶体抑制剂诱导大鼠黑质变性及大鼠运动行为改变,探讨蛋白酶体功能下降在帕金森病发病机制中的作用。方法将蛋白酶体抑制剂立体定向注射入大鼠左侧黑质致密部,对照组注射等体积的生理盐水。观察大鼠自主行为和阿朴吗啡诱导的旋转行为的改变。开野实验观察大鼠自发运动行为改变。免疫组织化学法观察黑质致密部及纹状体内酪氨酸羟化酶的表达。结果Lactacystin组大鼠给药一周后出现自发性活动减少,动作缓慢,震颤、对外界刺激不自主竖毛,且症状逐步加重;阿朴吗啡可诱导出向健侧的旋转运动。开野实验中,Lactacystin组大鼠自发运动行为出现改变。三周后黒质部位酪氨酸羟化酶免疫阳性细胞及纹状体内酪氨酸羟化酶免疫阳性神经纤维减少。结论蛋白酶体抑制剂Lactacystin单侧黑质致密部微量注射可以诱导大鼠黑质变性并出现运动行为改变,蛋白酶体抑制剂在帕金森病动物模型制备上有潜在价值,蛋白酶体功能下降可能在帕金森病发病机制中起重要作用。Objective To observe the nigral degeneration and motor behavior changes induced by proteasome inhibitor in the substantia nigra, and to investigate the role of proteasomal dysfunction in the pathogenesis of Parkinson＇s disease. Methods Lactacystin, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigral pars compacta of rats. Equal volume of saline were injected in control group. The spontaneous behavioral abnormalities, apomorphine-induced contralateral rotations of rats and the spontaneous motor behavioral changes in the open-field were observed. The expressions of tyrosine hydroxylase in substantia nigra and striatum was investigated by immunohistochemistry. Results The rats became progressively bradykinetic and displayed contralateral head tilting, tremor and apomorphine --induced contralateral rotation 7 days after Lactacystin injection. The spontaneous motor behavior of rats in Lactacystin group changed in open--field test. The numbers of TH--positive cells in left SNc and TH -- positive nerve fibers in left striatum in Lactacystin group significantly de- creased. Conclusion Lactacystin, a selective proteasome inhibitor, unilaterally injected stereotaxically into the left substantia nigral pars compacta of rats, can induce the degeneration of substantia nigra and motor behavioral changes of rats. Lactacystin may be used for the establishment of new PD animal model. Proteasomal dysfunction may play an important role in the pathogenesis of PD.

关 键 词：帕金森病 LACTACYSTIN 黑质 行为 

分 类 号：R742.5[医药卫生—神经病学与精神病学]