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槲皮素预处理对 MPP 暴露的 SH-SY5Y 细胞中 γH2AX、COX-2 的抑制作用及抗氧化酶的调节

Inhibition of γH2AX, COX-2 and regulation of antioxidant enzymes in MPP-exposed SH-SY5Y cells pre-treated with rutin.

机构信息

Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville, 7535, South Africa.

Department of Anatomy, School of Basic Medical Sciences, University of Benin, Edo State, Nigeria.

出版信息

Metab Brain Dis. 2021 Oct;36(7):2119-2130. doi: 10.1007/s11011-021-00746-z. Epub 2021 May 12.

DOI:10.1007/s11011-021-00746-z
PMID:33978902
Abstract

Many plant-derived bioactive compounds such as rutin are reportedly effective in attenuating neuronal death in most neurodegenerative disorders. Parkinson's disease (PD) is characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra of the midbrain, and has previously been modelled in-vitro through the specific neurotoxic activity of 1-methyl-4-phenylpyridinium (MPP) on dopaminergic neurons. Rutin is a bioflavonoid with multiple pharmacological effects, and this study investigated the neuroprotective effects of rutin in the human dopaminergic SH-SY5Y cell line using the neurotoxin MPP. SH-SY5Y cells pretreated with rutin, were exposed to MPP and evaluated for cell viability, nitric oxide (NO), reactive oxygen species (ROS) and antioxidant enzymes activities. In addition, western blot techniques were used to determine the protein expression levels of γH2AX and COX-2. Rutin significantly attenuated MPP-induced loss of cell viability, mitigated ROS and NO production and inhibited the disruption of antioxidant enzymes activity. It was also observed that rutin significantly reduced protein expression levels of γH2AX and COX-2 in SH-SY5Y cells treated with MPP. Taken together, findings from this study tend to suggest that rutin is a promising neuroprotective compound for the treatment of PD through its effects on some of the mechanisms that characterize this neurodegenerative disease.

摘要

许多植物源性生物活性化合物,如芦丁,据称可有效减轻大多数神经退行性疾病中的神经元死亡。帕金森病(PD)的特征是中脑黑质中多巴胺能神经元的逐渐退化,先前已通过特定的神经毒性活性 1-甲基-4-苯基吡啶(MPP)对多巴胺能神经元在体外进行建模。芦丁是一种具有多种药理作用的类黄酮,本研究通过 MPP 研究了芦丁在人多巴胺能 SH-SY5Y 细胞系中的神经保护作用。用芦丁预处理的 SH-SY5Y 细胞暴露于 MPP 中,并评估细胞活力、一氧化氮(NO)、活性氧(ROS)和抗氧化酶活性。此外,还使用 Western blot 技术来确定 γH2AX 和 COX-2 的蛋白表达水平。芦丁可显著减轻 MPP 诱导的细胞活力丧失,减轻 ROS 和 NO 的产生,并抑制抗氧化酶活性的破坏。还观察到芦丁可显著降低 MPP 处理的 SH-SY5Y 细胞中 γH2AX 和 COX-2 的蛋白表达水平。总之,本研究的结果表明,芦丁通过其对一些特征性神经退行性疾病机制的影响,可能成为治疗 PD 的有前途的神经保护化合物。

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