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白藜芦醇通过诱导线粒体自噬缓解氧/葡萄糖剥夺/复氧诱导的神经元损伤。

Resveratrol alleviates oxygen/glucose deprivation/reoxygenation‑induced neuronal damage through induction of mitophagy.

机构信息

Department of Geriatrics, Yichang Central People's Hospital, Yichang, Hubei 443003, P.R. China.

The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei 443003, P.R. China.

出版信息

Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11711. Epub 2020 Nov 25.

Abstract

Resveratrol confers neuroprotective effects in cerebral ischemia; however, the involvement of mitophagy in the neuroprotective function of resveratrol remains unclear. The aim of the present study was to investigate whether resveratrol exerts neuroprotective effects on primary cortical neurons subjected to oxygen/glucose deprivation/reoxygenation (OGD/R) via modulating mitophagy. The data demonstrated that resveratrol at 1‑10 M during reoxygenation improved cell viability and suppressed apoptosis following OGD/R in a concentration‑dependent manner. Moreover, resveratrol alleviated OGD/R‑induced loss of mitochondrial membrane potential and excessive oxidative stress. Confocal imaging of LC3 and TOM20 antibody‑labeled mitochondria, as well as western blot analysis, demonstrated that mitophagy was further enhanced following resveratrol treatment. In addition, resveratrol was revealed to stimulate the phosphatase and tensin homolog‑induced kinase 1/Parkin pathway. Mitophagy inhibition then inhibited the protective effects of resveratrol. These results indicated that resveratrol exerts its protective effects against OGD/R damage, at least in part, by promoting mitophagy.

摘要

白藜芦醇可发挥脑缺血保护作用;然而,其在白藜芦醇发挥神经保护功能过程中对细胞自噬的影响尚不清楚。本研究旨在探讨白藜芦醇是否通过调控细胞自噬对氧/葡萄糖剥夺/复氧(OGD/R)诱导的原代皮质神经元发挥神经保护作用。研究数据表明,在复氧期间,白藜芦醇在 1-10 μM 浓度范围内可呈浓度依赖性方式提高细胞活力并抑制 OGD/R 后的细胞凋亡。此外,白藜芦醇可减轻 OGD/R 诱导的线粒体膜电位丧失和过度氧化应激。LC3 和 TOM20 抗体标记的线粒体共聚焦成像以及 Western blot 分析表明,白藜芦醇处理后细胞自噬进一步增强。此外,白藜芦醇可刺激磷酸酶和张力蛋白同源物诱导的激酶 1/ Parkin 通路。自噬抑制则抑制了白藜芦醇的保护作用。这些结果表明,白藜芦醇通过促进细胞自噬对 OGD/R 损伤发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ba9/7716397/657b2db0dc27/mmr-23-01-11711-g00.jpg

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