State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xiannongtan Street, Xuanwu District, Beijing, 100050, People's Republic of China.
Neurochem Res. 2013 Aug;38(8):1553-60. doi: 10.1007/s11064-013-1055-7. Epub 2013 May 7.
Parkinson's disease (PD) is a common neurodegenerative disease, and its etiology remains obscure. Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in increasing the risk of developing PD and inflammation is the early incident during the process of PD. In this study, we measure the pro-inflammatory cytokines by enzyme-linked immunosorbnent assay and RT-PCR methods; analyze the reactive oxygen species by DCFH-DA; detected nuclear factor κB (NFκB) translocation by western blot and immunofluorescence methods; and analyze the phosphorylation of mitogen-activated protein (MAP) kinase and protein level of Nurr1 by western blot. Results showed that rotenone could induce tumor neurosis factor α (TNFα) and interleukin 1β (IL-1β) release from BV-2 cells, enhance TNFα and IL-1β mRNA levels in substantia nigra lesioned by rotenone; also, rotenone could increase the phosphorylation of inhibitor of κB (IκB), extracellular regulated protein kinase , c-Jun N-terminal kinase, p38 MAP kinases and promote p65 subunit of NFκB translocation to nuclear; at the same time, rotenone could decrease the protein level of Nurr1 in nuclear. So, rotenone exerted toxicity through activating microglia, and its mechanism might be associated with NFκB signal pathway.
帕金森病（PD）是一种常见的神经退行性疾病，其病因仍不清楚。越来越多的证据表明，环境因素如接触杀虫剂等在增加 PD 发病风险方面起着重要作用，而炎症是 PD 发生过程中的早期事件。在这项研究中，我们通过酶联免疫吸附试验和 RT-PCR 方法测量促炎细胞因子；通过 DCFH-DA 分析活性氧；通过 Western blot 和免疫荧光方法检测核因子κB（NFκB）易位；通过 Western blot 分析丝裂原激活蛋白（MAP）激酶的磷酸化和 Nurr1 蛋白水平。结果表明，鱼藤酮可诱导 BV-2 细胞释放肿瘤坏死因子-α（TNFα）和白细胞介素 1β（IL-1β），增强鱼藤酮损伤的黑质中 TNFα 和 IL-1β 的 mRNA 水平；同时，鱼藤酮可增加 IκB 的磷酸化、细胞外调节蛋白激酶、c-Jun N-末端激酶、p38 MAP 激酶，并促进 NFκB 的 p65 亚基向核内易位；同时，鱼藤酮可降低核内 Nurr1 的蛋白水平。因此，鱼藤酮通过激活小胶质细胞发挥毒性作用，其机制可能与 NFκB 信号通路有关。
