单侧损伤大鼠黑质纹状体多巴胺能通路新纹状体多巴胺受体在光镜、电镜下的变化  

A light and electron microscopic study on changes of dopamine receptors in the rat neostriatum after unilateral lesion of the nigrostriatal dopaminergic pathway

作　　者：曾宪智[1] 蔡青[2] 高尔静[2] 徐群渊[2] 

机构地区：[1]嘉兴学院医学院,嘉兴314000 [2]首都医科大学北京神经科学研究所,北京100069

出　　处：《解剖学报》2009年第5期702-708,共7页Acta Anatomica Sinica

基　　金：国家重点基础研究发展计划(973)资助项目(2006CB500700)

摘　　要：目的探讨帕金森病多巴胺受体在疾病状态下超微结构上的分布变化。方法用免疫组织化学和包埋前免疫胶体金电镜方法,研究6-羟多巴胺(6-OHDA)单侧损毁大鼠的多巴胺能通路帕金森病模型,在4周和16周时纹状体D1多巴胺受体(D1R)和D2多巴胺受体(D2R)的变化。结果光镜观察显示,4周时损伤侧纹状体D1R减少,在电镜下可见该减少在棘突而不是树突或胞体;16周时,光镜下虽然损伤侧D1R恢复到损伤对侧水平,但在电镜下却可见损伤侧棘突和树突D1R数量减少,而胞体的D1R数量却明显增多。4周和16周时损伤侧D2R在光镜下均增多,在电镜下D2R胶体金颗粒增多主要发生在棘突和树突而不是胞体。另外,损伤后4周和16周,可见这两种受体的金颗粒更多地位于突触外。结论这些变化可能在帕金森病症状发生发展及左旋多巴治疗副作用的产生中起重要作用。Objective There have been robust of reports about quantity changes of dopamine receptors but there has no report describing the distribution changes of dopamine receptors at ultrastructural level in Parkinson disease until now. As whether those receptors are functional and the magnitude of their function is closely related to their distribution, it is necessary to study their distribution changes at ultrastructural revel under the disease situation. Methods Changes of striatal dopamine D1 receptors （D1R） and D2 dopaminc receptors （D2R） in rats 4 weeks and 16 weeks after 6-hydroxydopamine （6-OHDA） unilateral lesion nigro-striatal dopaminergic pathway were studied by immunohistochemical and pre-imbedding immunogold electron microscopic methods. Results Four weeks after lesion, striatal D1R ipsilateral to lesion side decreased as observed under light microscope. The decrease happened at spines but not dendrites or cell bodies under electron microscope. 16 weeks after lesion, although the degree of striatal D1R ipsilateral to lesion side returned to the degree contralateral to the lesion side at light microscopic level, the amount of D1R decreased at spines and dendrite but increased significantly at cell bodies at electron microscopic level. Both 4 and 16 weeks after lesion, striatal D2R increased ipsilateral to lesion side under light microscope, the increased D2R particles were found at spines and dendrites but not cell bodies. Moreover, more gold particles of the two receptors were found at the extrasynaptic site both 4 weeks and 16 weeks after lesion. Conclusion These changes might play important roles in the onset and development of Parkinson＇ s disease and mechanism of side effect of levodopa therapy.

关 键 词：帕金森病 多巴胺受体 超微结构 免疫胶体金 免疫组织化学 大鼠 

分 类 号：Q189[生物学—神经生物学]