CDK5在左旋多巴诱发异动症形成中作用的研究  

The role of changes of CDK5 expression in the pathogenesis of levodopa-induced dyskinesias

作　　者：牛轶瑄[1] 孙圣刚[1] 魏桂荣[1] 张允建[1] 徐岩[1] 曹学兵[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：《中风与神经疾病杂志》2007年第4期413-415,共3页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金资助项目(No30300114)

摘　　要：目的研究纹状体区CDK5的表达变化在左旋多巴诱发的异动症(LID)形成中所起的作用。方法以Roscovitine(CDK5拮抗剂)治疗LID大鼠,观察大鼠行为学改变并用免疫印迹技术检测其纹状体区CDK5、Thr-34位点和Thr-75位点磷酸化的DARPP-32蛋白表达的变化。结果LID大鼠毁损侧纹状体区CDK5表达量和Thr-34位点磷酸化的DARPP-32水平均较非LID组显著增高,而Thr-75位点磷酸化的DARPP-32表达与非LID组相比无显著差异。经Roscovitine治疗后,前两者表达均显著下降,而后者较LID组显著增加,同时大鼠异常不自主运动明显减少。结论DARPP-32的Thr-34位点的磷酸化水平的增高与LID的形成关系密切。CDK5的表达增强与机体稳定内环境的代偿性反应有关。Objective To study the role of changes of CDK5 expression in striatum in the pathogenesis of levodopa-induced dyskinesias （LID）. Methods Roscovitine （CDK5 antagonist） was injected into striatum of LID rats. Western blot was used to measure the expression of CDK5 and phosphorylations of DARPP-32 at Thr-34 and Thr-75 in striatum and the behavior changes were observed. Results Phospho-Thr34 DARPP-32 and the expression of CDK5 increased significantly in LID group compared to non-LID group （P〈0.05） ,but the changes of phos- pho-Thr75 DARPP-32 were not significant （P〉0.05）. After administration of roscovitine, abnormal involuntary movement （AIM） was decreased and the expression of CDK5 and phospho-Thr75 DARPP-32 in striatum were de- creased,phospho-Thr34 DARPP-32 was increased significantly（P〈0.05）. Conclusions Increased phospho-Thr34 DARPP-32 in striatum plays a key role in LID occurrence. CDK5 overexpression could involved in a negative feedback homeostatic mechanism invoked in response to LID.

关 键 词：异动症 CDK5 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]