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帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究
引用本文:吴娜,杨新新,宋璐,刘振国. 帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究[J]. 中华老年医学杂志, 2009, 30(8): 327-331. DOI: 10.3760/cma.j.issn.0254-9026.2011.04.019
作者姓名:吴娜  杨新新  宋璐  刘振国
作者单位:上海交通大学医学院附属新华医院神经内科,200092;
基金项目:上海市科委纳米技术专项项目上海市科委基础研究重点项目上海市教委科研创新重点项目上海市白玉兰科技人才基金国家自然科学基金
摘    要:Objective To investigate the relationship between G protein-coupled receptor kinase 6 (GRK6) and N-methyl-D-aspartate (NMDA) receptor in the mechanism study underlying motor complications in Parkinson's disease (PD).Methods The rat models (n= 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n= 10,intraperitoneal injection of levodopa for 23 d),MK-801 treatment group (n= 10,intraperitoneal injection of MK-801 at day23 after intraperitoneal injection with levodopa for 22 days) and PD group (n= 5,intraperitoneal injection of vitamin C).Another 5 rats were served as controls (sham-operation group).The behavior changes of rats in MK-801 treatment group were observed,and the expression of GRK6 in the striate of rats was detected by immunohistochemistry and Western blot.Results After the chronic treatment with levodopa methyl ester,PD rats displayed abnormal involuntary movements,which was similar to levodopainduced dyskinesia in PD patients.Immunohistochemistry showed that GRK6-positive cells of lesion side were decreased in LID rats as compared with PD rats [(3.23±0.41 ) × 103 vs.(4.81 ± 1.31 ) ×103,P<0.01].Rats in MK-801 treatment group displayed the decreased AIM scores and increased peak rotation,and the increased GRK6-positive cells of lesion side as compared with LID rats (P<0.05).Western blot showed that the levels of GRK6 was 83.7% ±2.1% in PD group (presented as lesion side/unlesion side),76.8% ± 2.2% in LID group and 91.1% ± 2.7% in MK-801 treatment group (intergroups comparison:all P<0.05).These results were in accordance with the results of immunohistochemistry.Conclusions Antagonist of NMDA receptor can be used to reduce the motor complications in rats.It may be due to increased GRK6 which inhibits the overactivation of glutamic acid receptors.

关 键 词:帕金森病   左旋多巴   受体,G蛋白偶联   蛋白激酶类   受体,N-甲基-D-天冬氨酸   

Relationship between G protein-coupled receptor kinase 6 and N-methyl-D-aspartate receptor in the mechanism study underlying motor complications in Parkinson's disease
WU Na,YANG Xin-xin,SONG Lu,LIU Zhen-guo. Relationship between G protein-coupled receptor kinase 6 and N-methyl-D-aspartate receptor in the mechanism study underlying motor complications in Parkinson's disease[J]. Chinese Journal of Geriatrics, 2009, 30(8): 327-331. DOI: 10.3760/cma.j.issn.0254-9026.2011.04.019
Authors:WU Na  YANG Xin-xin  SONG Lu  LIU Zhen-guo
Abstract:
Keywords:Parkinson diseaseLevodopaReceptors  G-protein-coupledProtein kinasesReceptor  N-Methyl-D-aspartate
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