He Yi, Imam Syed Z, Dong Zaojun, Jankovic Joseph, Ali Syed F, Appel Stanley H, Le Weidong
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurochem. 2003 Sep;86(6):1338-45. doi: 10.1046/j.1471-4159.2003.01938.x.
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.
鱼藤酮是一种广泛使用的杀虫剂，它会使大鼠出现一种综合征，在行为和病理方面都类似于帕金森病的症状。本研究评估了一氧化氮在鱼藤酮诱导的黑质 - 纹状体损伤中的作用。给大鼠连续40天施用鱼藤酮后，黑质 - 纹状体通路出现中度但显著的损伤，表现为纹状体多巴胺水平降低47%以及黑质酪氨酸羟化酶免疫阳性神经元损失28%。此外，观察到纹状体中烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）阳性细胞数量显著增加（37%），同时一氧化氮合酶（NOS）活性增加83%，3-硝基酪氨酸（3-NT）的生成也显著增加。黑质中NADPH-d染色的光密度显著增加（45%），NOS活性增加（72%）。此外，施用神经元型NOS抑制剂7-硝基吲唑可显著减弱增加的NOS活性和3-NT生成，并为鱼藤酮诱导的黑质 - 纹状体损伤提供显著保护。我们的数据表明，长期施用鱼藤酮可导致黑质 - 纹状体系统的显著损伤，这是由一氧化氮生成增加介导的。
