6-羟基多巴胺帕金森病大鼠模型的制作和行为学评价  

Preparation and Behavior Evaluation of the 6-OHDA-Lesioned Rat Model of Parkinson' s Disease

作　　者：张耀芬[1] 段德义[1] 徐群渊[1] 

机构地区：[1]首都医科大学北京神经科学研究所

出　　处：《解剖科学进展》2005年第1期49-53,共5页Progress of Anatomical Sciences

基　　金：国家重点基础研究规划-脑功能和脑重大疾病的基础研究(G1999054008);北京市自然科学基金重点项目(7011001);北京市科委科技计划项目(9555101200)

摘　　要：6 羟基多巴胺能与多巴胺竞争性结合多巴胺转运体而进入细胞,通过诱发氧化应激反应、抑制 线粒体功能等选择性地损害多巴胺能神经元。将这种神经毒素于大鼠中脑黑质注射,神经元发生损伤至多巴 胺耗竭;于纹状体注射神经元损伤较慢呈渐进性过程。在这些情况下,神经元丢失程度都与注射部位相关。 在大鼠第三脑室注射能诱发出与人类极为相似的神经元退变模式,即中脑内不同区域的DA能神经元因敏感 性不同损伤程度也不同。大鼠模型的行为学评估包括药物诱发试验和非药物诱发试验,前者使用最多,而后 者种类较多。两种方法结合使用能使评估结果更有效、可靠。6-hydroxydopamine (6-OHDA), a neurotoxin, is uptaken and accumulated in the dopaminergic neurons by competitively binding to the dopamine transporter on the cell membrane, and therefore, it selectively damages the dopaminergic neurons through induction of autoxidation and inhibition of the mitochondrial function to produce reactive oxygen species and to deplete the intracellular ATP. Injection of 6-OHDA into the substantia nigra leads to comparatively acute and extensive dopamine depletions;while injected into the striatum, it produces a slow and progressive degenerative process. In these two cases, the extent of neuronal loss is correlated with the injection sites.After cerebroventricular administration, 6-OHDA can produce a neurodegeneration process similar to that observed in the brains of PD patients. This process is able to show various degrees of neuronal loss in the distinct subregions of the midbrain because the neurons in these subregions are diversely susceptible to 6-OHDA. The evaluation of the behavior includes the drug-induced test and the non-drug-induced test.The former is most frequently used in the laboratory, and the latter comprise many sorts. The combination of these two methods will be more effective and reliable.

关 键 词：神经元 大鼠模型 6-羟基多巴胺 注射 诱发 行为学 帕金森病 评估结果 过程 竞争性 

分 类 号：Q421[生物学—神经生物学] R742[生物学—生理学]