Role of nitric oxide in rotenone-induced nigro-striatal injury
Role of nitric oxide in rotenone-induced nigro-striatal injury
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DOI：
10.1046/j.1471-4159.2003.01938.x
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发表时间：
2003-09-01
影响因子：
4.7
通讯作者：
Le, WD
中科院分区：
文献类型：
--
作者：
He, Y;Imam, SZ;Le, WD
鱼藤酮是一种广泛使用的杀虫剂，它会在老鼠身上引起一种综合症，在行为和病理上都模仿帕金森病的症状。本研究评估了一氧化氮在鱼藤酮诱导的黑纹状体损伤中的作用。鱼藤酮给药40天后，大鼠的黑质纹状体通路出现中度但明显的损伤，纹状体多巴胺水平下降47%，黑质酪氨酸羟化酶免疫阳性神经元减少28%。此外，纹状体中烟酰胺腺嘌呤二核苷酸磷酸二磷酶（NADPH-d）阳性细胞数量显著增加（37%），一氧化氮合酶（NOS）活性增加83%，3-硝基酪氨酸（3-NT）产量显著增加。NADPH-d染色光密度显著增加（45%），黑质NOS活性显著增加（72%）。此外，给予神经元NOS抑制剂7-硝基茚唑可显著降低NOS活性和3-NT的产生，并对鱼藤酮诱导的黑质纹状体损伤有显著保护作用。我们的数据表明，慢性鱼藤酮管理可导致显著损伤黑纹状体系统，介导增加生成一氧化氮。
Rotenone, a widely used pesticide, causes a syndrome in rats that mimics, both behaviorally and pathologically, the symptoms of Parkinson's disease. The present study evaluated the role of nitric oxide in rotenone-induced nigro-striatal injury. After administration of rotenone in rats for 40 days, there was a moderate but significant injury of the nigro-striatal pathway indicated by a 47% decrease in striatal dopamine levels and a 28% loss of substantia nigra tyrosine hydroxylase-immunopositive neurons. Furthermore, a significant (37%) increase in the number of cells positive for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the striatum was observed, accompanied by a 83% increase in nitric oxide synthase (NOS) activity and a significant increase in the production of 3-nitrotyrosine (3-NT). There was a significant increase (45%) in the optical density of NADPH-d staining and an increase (72%) in NOS activity in the substantia nigra. Moreover, administration of the neuronal NOS inhibitor 7-nitroindazole significantly attenuated the increased NOS activity and 3-NT production, and provided significant protection against rotenone-induced nigro-striatal injury. Our data suggest that chronic rotenone administration can lead to significant injury to the nigro-striatal system, mediated by increased generation of nitric oxide.