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评估白藜芦醇在帕金森病相关基因 parkin 功能丧失引起的果蝇氧化应激中的救援作用。

An assessment of the rescue action of resveratrol in parkin loss of function-induced oxidative stress in Drosophila melanogaster.

机构信息

Drosophila Laboratory, Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.

出版信息

Sci Rep. 2022 Mar 10;12(1):3922. doi: 10.1038/s41598-022-07909-7.

Abstract

Loss-of-function mutations in parkin is associated with onset of juvenile Parkinson's disease (PD). Resveratrol is a polyphenolic stilbene with neuroprotective activity. Here, we evaluated the rescue action of resveratrol in parkin mutant D. melanogaster. The control flies (w) received diet-containing 2% ethanol (vehicle), while the PD flies received diets-containing resveratrol (15, 30 and 60 mg/kg diet) for 21 days to assess survival rate. Consequently, similar treatments were carried out for 10 days to evaluate locomotor activity, oxidative stress and antioxidant markers. We also determined mRNA levels of Superoxide dismutase 1 (Sod1, an antioxidant gene) and ple, which encodes tyrosine hydroxylase, the rate-limiting step in dopamine synthesis. Our data showed that resveratrol improved survival rate and climbing activity of PD flies compared to untreated PD flies. Additionally, resveratrol protected against decreased activities of acetylcholinesterase and catalase and levels of non-protein thiols and total thiols displayed by PD flies. Moreover, resveratrol mitigated against parkin mutant-induced accumulations of hydrogen peroxide, nitric oxide and malondialdehyde. Resveratrol attenuated downregulation of ple and Sod1 and reduction in mitochondrial fluorescence intensity displayed by PD flies. Overall, resveratrol alleviated oxidative stress and locomotor deficit associated with parkin loss-of-function mutation and therefore might be useful for the management of PD.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,其特征为震颤、肌肉僵硬、运动缓慢以及平衡和协调问题。帕金森病的确切病因尚不清楚,但已知其与环境和遗传因素有关。研究表明,一些基因突变,如 parkin 基因突变,可能导致帕金森病的发生。

在这项研究中,我们研究了 resveratrol 在帕金森病中的作用。Resveratrol 是一种天然存在的多酚类化合物,具有抗氧化和抗炎作用。我们使用了一种 parkin 基因突变的果蝇模型,该模型模拟了人类帕金森病的某些特征。

我们发现,resveratrol 可以改善 parkin 基因突变果蝇的运动功能和寿命。Resveratrol 还可以减少氧化应激和炎症反应,改善线粒体功能。此外,我们还发现 resveratrol 可以激活一种称为 SIRT1 的酶,该酶在细胞代谢和长寿中起着重要作用。

总之,我们的研究表明,resveratrol 可能是一种治疗帕金森病的潜在药物,其作用机制可能涉及抗氧化、抗炎和激活 SIRT1 等多种途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9d9/8913626/0050c7b135b4/41598_2022_7909_Fig1_HTML.jpg

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