左旋多巴诱发异动症大鼠纹状体区P38及GAP-43表达的变化  

Study on P38 and GAP-43 Expressions in Striatum of L-dopa Induced Dyskinesias Rats

作　　者：王岚[1] 曹学兵[1] 孙圣刚[1] 徐岩[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内科,湖北武汉430022

出　　处：《中国神经免疫学和神经病学杂志》2005年第1期10-13,25,共5页Chinese Journal of Neuroimmunology and Neurology

摘　　要：目的　观察帕金森病(Parkinson disease, PD)大鼠经慢性间断性左旋多巴(levodopa,L- dopa)治疗后纹状体区域突触功能的变化。方法　 6 羟多巴胺 (6 OHDA)脑立体定位注射制备偏侧PD大鼠模型,复方L dopa甲酯治疗4周[按体重20 mg/(kg·d),分2次进行腹腔注射]建立异动症(levodopa induced dyskinesias,LID)大鼠模型,采用免疫组化方法检测 PD组和 LID组纹状体内突触素(synaptophysin, P38)及生长相关蛋白(growth associated protein, GAP 43)的表达。结果　 PD 大鼠损毁侧 P38 免疫反应阳性颗粒的数密度[(0. 002 1±0 000. 5)个/μm2]和面密度(0. 045±0.01)均明显高于健侧[分别为(0 .015 0±0. 000 6)个/μm2, (0 027±0 .009)](P<0 .01),GAP- 43阳性颗粒面密度(0. 015±0. 000 3)高于健侧(0. 01±0 .000 27)(P<0. 05);LID大鼠经L dopa治疗后两者表达进一步增多,与PD组大鼠损毁侧相比差异有显著性(均 P<0 .05)。结论　慢性L dopa治疗进一步促进了PD大鼠纹状体区域P38及GAP -43的高表达,可能涉及皮质纹状体病理性长时程增强的突触前机制,提示皮质 纹状体环路的突触可塑性与LID发生密切相关。Objective To explore the synaptic functional plasticity of striatal neuron in rats with Parkinson disease(PD) and levodopa- induced dyskinesias(LID). Methods The PD rats were prepared by unilateral injection with 6-OHDA in the substantia nigra and then treated with levodopa\[20 mg/(kg· d)\] twice a day for 4 weeks. The normal rats was accepted the same levodopa pulsative treatment as the control group. Immunocyto chemistry was carried out to test the changes of synaptophysin(P38) and growth-associated protein(GAP-43) expressions in the striatum. Results In PD group, the amount and dimension density of P38 immunopositive terminals increased in striatum as compared with control group(P<0.01), and the dimension density of GAP-43 immunostaining increased as well(P<0.05). But treatment with L-dopa promoted further the high expression of P38 and GAP-43,they were significantly higher than the PD group(P<005). Conclusions Chronic intermittent levodopa treatment improved expression of synaptic GAP-43 and synaptic vesicle proteins which probably involved in the pre-synaptic mechanisms of long-term potentiation at cortico-striatalprojection. These results suggest that the synaptic plasticity of corticostriatal synapse may play an important role in the development of LID.

关 键 词：帕金森病 左旋多巴诱发异动症 突触可塑性 

分 类 号：R742.5[医药卫生—神经病学与精神病学]