DARPP-32磷酸化状态与左旋多巴诱发异动症形成间关系的研究  

The role of Changes in the state of phosphorylation of DARPP-32 in rats with levodopa-induced dyskinesias

作　　者：牛轶瑄[1] 曹学兵[1] 魏桂荣[1] 徐岩[1] 管强[1] 孙圣刚[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经科,湖北武汉430022

出　　处：《脑与神经疾病杂志》2008年第1期1-4,共4页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金资助项目(30300114)

摘　　要：目的:研究纹状体区DARPP-32磷酸化水平变化和直接通路活动的改变在左旋多巴诱发的异动症(LID)形成中所起的作用。方法:以SCH23390(D1受体拮抗剂)治疗LID大鼠,观察LID大鼠的行为学改变,并用逆转录聚合酶链反应技术检测LID大鼠纹状体区前强啡肽原(PDyn)基因mRNA的表达情况,免疫印迹技术检测纹状体内DARPP-32蛋白Thr-34位点和Thr-75位点磷酸化修饰水平的变化。结果:LID大鼠纹状体区PDyn mRNA基因表达和磷酸化的Thr-34位点DARPP-32水平较对照组均明显增高,Thr-75位点磷酸化无显著改变。经SCH23390治疗后,LID大鼠异常不自主运动明显减少,PDyn基因表达和Thr-34位点磷酸化水平降低,Thr-75位点磷酸化水平升高。结论:大鼠纹状体区PDyn基因表达和Thr-34位点磷酸化水平的升高与LID的形成有关,提示直接通路活动异常及基底节环路功能异常参与了LID的发生。Objective： To study the role of changes in the state of phosphorylation of DARPP-32 and in the direct pathway in the pathogenesis of levodopa-induced dyskinesias（LID）. Methods：The LID rats were treated with SCH 23390 （a doparnine D1 antagonist）. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to measure the expres- sions of PDyn mRNA in striatum, western blot was used to measure the phosphorylation levels of DARPP-32 at Thr34 and Thr75 in striatum, the behavior changes of LID rats were observed also. Results：levels of phospho-Thr34 DARPP-32 protein and PDyn mRNA expression in striatum increased significantly in LID group （P〈0.05）, but the changes of phospho-Thr75 DARPP-32 were not significant compared with control group （P〉0.05）. After treatment with SCH23390, abnormal involuntary movement （AIM） decreased, the expression of PDyn mRNA and phospho-Thr34 DARPP-32 protein in striatum decreased, phospho-Thr75 DARPP-32 protein increased significantly（P〈0. 05）. Conclusion： LID is associated with high levels of phospho-Thr34 DARPP-32 and over expression of PDyn mRNA,which indicates abnormal activity in the direct pathway and the basal ganglia circuit involving in the occurrence of LID.

关 键 词：异动症 帕金森病 DARPP-32 磷酸化修饰 

分 类 号：R742.5[医药卫生—神经病学与精神病学]