β-arrestinl参与MK-801治疗帕金森病异动症的研究  

β-arrestinl mediates the effect of MK-801 on levodopa-induced dyskinesia in Parkinson＇ s disease

作　　者：吴娜[1] 宋璐[1] 杨新新[1] 刘振国[1] 

机构地区：[1]上海交通大学医学院附属新华医院神经内科,200092

出　　处：《中华神经科杂志》2011年第9期597-601,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（81071025）;上海市科委纳米技术专项资助项目（0952nm03700）;上海市科委基础研究重点资助项目（09JC1411000）;上海市教委科研创新重点资助项目（10ZZ72）;上海市白玉兰科技人才基金资助项目（1009B097）

摘　　要：目的探讨MK-801缓解帕金森病（PD）异动症的治疗机制。方法建立PD运动并发症大鼠模型，25只大鼠随机分为3组：异动症（LID）组10只、MK-801处理组10只、PD组5只，另设假手术组5只为对照组。观察MK-801治疗左旋多巴诱导的异动症大鼠模型的行为学变化，并采用免疫组织化学方法和Western blot印迹法检测大鼠纹状体区β-arrestinl的表达情况。结果MK-801处理后，LID大鼠模型异常不自主运动评分降低和剂峰旋转行为减弱。免疫组织化学结果显示LID组损伤侧β-arrestinl阳性细胞指数[（2．95±0．44）×10^4]明显较未损伤侧[（3．78±0．37）×10^4]降低，差异有统计学意义（t=5．415，P〈0．05）。Western blot结果显示，PD模型组损毁侧与未损毁侧纹状体区β-arrestinl含量比值为81．02％±2．23％；LID组（64．88％±3．10％）蛋白表达量进一步减少，与PD组比较，差异有统计学意义（t=9．47，P〈0．01）；而MK-801组蛋白表达量增高至89．26％±1．90％。与LID组相比，差异有统计学意义（t=14．82，P〈0．01）。结论MK-801能缓解LID大鼠的行为学变化，其机制可能与β-arrestinl表达增多抑制了谷氨酸受体的过度活化有关。Objective To investigate the effect of MK-801 on levodopa-induced dyskinesia （LID） in Parkinson＇ s disease （PD）. Methods Rat models （ n = 25 ） of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia （LID） group （ n = 10）, MK- 801 treatment group （n = 10） and PD group （n = 5）. Another 5 rats were served as control group. The behaviors of LID rats treated with MK-801 were observed. Immunohistochemistry and Western blot analysis were used to determine the expression of β-arrestinl in the striate of rats. Results After MK-801 treatment, abnormal involuntary movement scores and peak turning were decreased in LID rats. Immunohistochemistry showed that β-arrestinl-positive cells of the lesioned side （（2. 95 ±0.44）×10^4） in LID rats were decreased compared to the contralateral side （ （ 3.78 ± 0. 37 ） ×10^4, t = 5.415, P 〈 0. 05 ）. Western blot showed that the levels of β-arrestinl in PD group （presented as lesioned side/contralateral side） were （81.02% ± 2. 23% ）. The levels of β-arrestinl （64. 88%± 3.10% ） were decreased in LID rats compared to PD rats （t = 9.47, P 〈 0. 01 ）. However, the levels of β-arrestinl （89. 26% ±1.90% ） were increased in MK-801-treated rats （t = 14. 82, P 〈 0. 01 ）. Conclusions MK-801 reduces LID in PD rats. The beneficial effect of MK-801 may be mediated through the increased expression of β-arrestinl which in turninhibits the overactivation of glutamate receptors.

关 键 词：帕金森病 运动失调 抑制蛋白类 地卓西平马来酸盐 

分 类 号：R742.5[医药卫生—神经病学与精神病学]