Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson's disease through inhibition of ROS-NO pathway

Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson's disease through inhibition of ROS-NO pathway
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DOI:
10.1016/j.biopsych.2007.04.020
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发表时间:
2007-12-15
影响因子:
10.6
通讯作者:
Zhao, Baolu
Zhao, Baolu
中科院分区:
医学1区
文献类型:
--
作者:
Guo, Shuhong;Yan, Jingqi;Zhao, Baolu

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背景:一氧化氮(NO)及其相关通路被认为在帕金森病(PD)的发病机制中起重要作用。我们的体外实验表明,绿茶多酚(GTP)可能通过抑制NO和活性氧(ROS)来保护多巴胺神经元。方法:采用免疫组织化学、末端脱氧核苷酸转移酶介导的dUTP Nick End标记法、电子自旋共振自旋捕获法、酶联免疫吸附法和分子生物学方法研究GTP对单侧6-羟基多巴胺(6-OHDA)处理大鼠PD模型的影响。结果:GTP对多巴胺能神经元的保护作用呈剂量依赖性,可防止中脑和纹状体6- ohda诱导的1)ROS和NO水平升高,2)脂质过氧化,3)亚硝酸盐/硝酸盐含量升高,4)诱导型一氧化氮合酶升高,5)蛋白结合3-硝基酪氨酸升高。此外,GTP治疗剂量依赖性地保留了中脑和纹状体的自由基清除能力。结论:这些结果支持GTP对6-OHDA的体内保护作用,并提示GTP治疗可能代表PD的神经保护治疗。
Background: Nitric oxide (NO) and related pathways are thought to play an important role in the pathogenesis of Parkinson's disease (PD). Our in vitro experiments suggested that green tea polyphenols (GTP) might protect dopamine neurons through inhibition of NO and reactive oxygen species (ROS).Methods: Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling assay, electron spin resonance spin trapping, enzyme linked immunosorbent assay, and molecular biological methods were used to investigate the effects of GTP in an unilateral 6-hydroxydopamine (6-OHDA)-treated rat model of PD.Results: GTP treatment dose-dependently protected dopaminergic neurons by preventing from midbrain and striatal 6-OHDA-induced increase in 1) both ROS and NO levels, 2) lipid peroxidation, 3) nitrite/nitrate content, 4) inducible nitric oxide synthase, and 5) protein-bound 3-nitro-tyrosine. Moreover, GTP treatment dose-dependently preserved the free radical scavenging capability of both the midbrain and the striatum.Conclusions: These results support the in vivo protection of GTP against 6-OHDA and suggest that GTP treatment might represent a neuroprotective treatment of PD.