鱼藤酮诱导大鼠帕金森样损伤及其机制的研究

中国药物警戒 ›› 2017, Vol. 14 ›› Issue (9): 513-517.

• 基础研究 • 下一篇

鱼藤酮诱导大鼠帕金森样损伤及其机制的研究

张秋双, 陈颖, 陈乃宏, 苑玉和^*

中国医学科学院药物研究所,北京 100050

收稿日期:2017-11-06 修回日期:2017-11-06 出版日期:2017-09-20 发布日期:2017-11-06
通讯作者: 苑玉和,女,博士,研究员,神经药理学。
作者简介:张秋双,女,在读硕士,神经药理学。
基金资助:
国家自然科学基金（81373997）：帕金森病创新药物研究

Parkinsonian Lesion in Rat Induced by Rotenone and its Possible Mechanism

ZHANG Qiu-shuang, CHEN Ying, CHEN Nai-hong, YUAN Yu-he^*

Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received:2017-11-06 Revised:2017-11-06 Online:2017-09-20 Published:2017-11-06

摘要/Abstract

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。

关键词: 帕金森病, 鱼藤酮, 立体定位, α-突触核蛋白, 神经炎症

Abstract: 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.

Key words: Parkinson's disease, rotenone, stereotaxic infusion, α-synuclein, neuroinflammation

中图分类号:

R965

张秋双, 陈颖, 陈乃宏, 苑玉和. 鱼藤酮诱导大鼠帕金森样损伤及其机制的研究[J]. 中国药物警戒, 2017, 14(9): 513-517.

ZHANG Qiu-shuang, CHEN Ying, CHEN Nai-hong, YUAN Yu-he. Parkinsonian Lesion in Rat Induced by Rotenone and its Possible Mechanism[J]. Chinese Journal of Pharmacovigilance, 2017, 14(9): 513-517.

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鱼藤酮诱导大鼠帕金森样损伤及其机制的研究

Parkinsonian Lesion in Rat Induced by Rotenone and its Possible Mechanism

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