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白藜芦醇在 MPTP 诱导的帕金森病样小鼠模型中的神经保护作用:可能通过抑制 SOCS-1 减少促炎反应。

Neuroprotective effects of resveratrol in an MPTP mouse model of Parkinson's-like disease: possible role of SOCS-1 in reducing pro-inflammatory responses.

机构信息

1Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy.

出版信息

Innate Immun. 2014 Apr;20(3):249-60. doi: 10.1177/1753425913488429. Epub 2013 Jun 13.

Abstract

In the present study we used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model to analyze resveratrol neuroprotective effects. The MPTP-induced PD model is characterized by chronic inflammation, oxidative stress and loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We observed that resveratrol treatment significantly reduced glial activation, decreasing the levels of IL-1β, IL-6 and TNF-α, as well as their respective receptors in the SNpc of MPTP-treated mice, as demonstrated by Western blotting, RT-PCR and quantitative PCR analysis. This reduction is related to possible neuroprotection as we also observed that resveratrol administration limited the decline of tyrosine hydroxylase-immunoreactivity induced in the striatum and SNpc by MPTP injection. Consistent with these data, resveratrol treatment up-regulated the expression of the suppressor of cytokine signaling-1 (SOCS-1), supporting the hypothesis that resveratrol protects DA neurons of the SNpc against MPTP-induced cell loss by regulating inflammatory reactions, possibly through SOCS-1 induction.

摘要

在本研究中,我们使用 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠模型来分析白藜芦醇的神经保护作用。MPTP 诱导的 PD 模型的特征是慢性炎症、氧化应激和黑质致密部(SNpc)中的多巴胺能(DA)神经元丧失。我们观察到白藜芦醇治疗显著减少小胶质细胞活化,降低 SNpc 中 IL-1β、IL-6 和 TNF-α及其各自受体的水平,这通过 Western blot、RT-PCR 和定量 PCR 分析得到证实。这种减少与可能的神经保护有关,因为我们还观察到白藜芦醇给药限制了 MPTP 注射诱导的纹状体和 SNpc 中酪氨酸羟化酶免疫反应性的下降。与这些数据一致,白藜芦醇治疗上调了细胞因子信号转导抑制因子-1(SOCS-1)的表达,支持白藜芦醇通过调节炎症反应来保护 SNpc 中的 DA 神经元免受 MPTP 诱导的细胞死亡的假说,可能通过 SOCS-1 诱导。

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