摘要
目的本实验从行为学、病理和生化三个方面对鱼藤酮损伤大鼠模型进行了评价,并讨论了帕金森病相关的发病机制。方法通过脑立体定位的方法向单侧大鼠黑质致密部区域注射鱼藤酮,诱导大鼠帕金森样损伤;其行为学损伤采用转棒实验和阿扑吗啡诱导旋转实验评价;病理异常通过免疫组化的方法评价;生化改变通过Western blot方法检测。结果单侧黑质致密部注射鱼藤酮可诱导大鼠出现行为学障碍,导致大鼠在阿扑吗啡诱导实验中出现单侧旋转的现象;病理生化结果显示,鱼藤酮可以引起多巴胺能神经元丢失,α-突触核蛋白磷酸化,小胶质细胞激活,肿瘤坏死因子和环氧合酶-2蛋白含量增加。结论鱼藤酮可以损坏多巴胺能神经元,诱导α-突触核蛋白磷酸化,激活小胶质细胞,增加肿瘤坏死因子和环氧合酶-2的蛋白含量,进而促进帕金森病的发生发展。
Objective To estimate the behavioral defects, pathological abnormalities, and biochemical changes after rotenone injection in rats, and study the associated mechanisms of Parkinson's disease (PD). Methods To induce the Parkinsonian lesions, rats got a stereotaxic injection of rotenone into the substantia nigra pars compacta. Behavioral performances were estimated by rotarod test and apomorphine induced rotation; pathological abnormalities were examined by immunohistochemistry; biochemical changes were detected by western blot. Results Unilateral stereotaxic infusion of rotenone led to behavioral defects of rats and resulted in rotations after rats treated by apomorphine. The pathological and biochemical results showed that rotenone had caused loss of dopaminergic neurons, phosphorylation of α-synuclein, activation of microglia, and increased protein content of tumor necrosis factor (TNF-α) and cyclooxygenase-2 (COX-2). Conclusion Rotenone may initiate and promote the neurodegeneration of PD by destroying dopaminergic neurons, inducing α-synuclein phosphorylation, activating microglia, and increasing the protein content of TNF-α and COX-2.
出处
《中国药物警戒》
2017年第9期513-517,共5页
Chinese Journal of Pharmacovigilance
基金
国家自然科学基金(81373997):帕金森病创新药物研究
关键词
帕金森病
鱼藤酮
立体定位
Α-突触核蛋白
神经炎症
Parkinson&#39
s disease
rotenone
stereotaxic infusion
α-synuclein
neuroinflammation