6-羟多巴诱导大鼠黑质的持续胶质细胞反应

6-HYDROXYDOPAMINE INDUCED A PERSISTENT GLIOSIS IN THE SUBSTANTIA NIGRA OF SD RAT

本研究将40μg6- 羟多巴注射到SD大鼠一侧纹状体制作Parkinson病动物模型,研究黑质反应性神经胶质增生在Par kinson病发病过程中的可能作用。筛选成功的模型大鼠,术后12周处死。应用免疫荧光双标记法检测模型大鼠黑质胶质细胞对多巴胺能神经元损伤的反应。结果显示:在注射后12周,损伤侧黑质仍然存在明显的星形胶质细胞反应和小胶质细胞激活。此外,小胶质小结和淋巴细胞浸润的存在提示在注射后12周的注射侧黑质内依然有多巴胺能神经元死亡。结论: 6 -羟多巴对大鼠黑质多巴胺能神经元的急性损伤可以通过胶质细胞反应从而对多巴胺能神经元产生长期的毒性作用。

To study the potential role of reactive gliosis in substantia nigra (SN) that may contribute to the pathogenesis of Parkinson's disease (PD), PD animal model was made by unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). The SD rats received unilateral intrastriatal injection of 40 μg of 6-OHDA. The succeed PD animals were killed 12 weeks after lesion. Double immunofluorescence method was used to observe the glial reaction in SN after dopaminergic neurons injury. A persistent, marked microglial activation and astrocytosis reaction were demonstrated in the SN. In addition, the microglial nodule and lymphocytes recruitment were also observed, suggesting that the dopaminergic neurons in lesioned SN still underwent cell death 12 weeks after 6-OHDA injection. Our data indicated that a single acute insult to the dopaminergic neurons in SN of SD rats by 6-OHDA injection could set in motion of self-sustained cascade of events with long-lasting deleterious effects mediated by reactive gliosis.