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白藜芦醇通过增强 Nrf-2 信号通路的激活作用,在不同时间点减轻氧葡萄糖剥夺/复氧诱导的神经元凋亡

Resveratrol Treatment in Different Time-Attenuated Neuronal Apoptosis After Oxygen and Glucose Deprivation/Reoxygenation via Enhancing the Activation of Nrf-2 Signaling Pathway In Vitro.

机构信息

1 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

2 Department of Neurology, Loma Linda University, School of Medicine, Loma Linda, CA, USA.

出版信息

Cell Transplant. 2018 Dec;27(12):1789-1797. doi: 10.1177/0963689718780930. Epub 2018 Jul 16.

Abstract

Recent studies have indicated that resveratrol has protective effects against cerebral ischemia/reperfusion injury. However, the best therapeutic time for resveratrol treatment after acute ischemic stroke remains unknown. We aim to investigate whether resveratrol, administrated at different times after neuronal oxygen and glucose deprivation/reoxygenation (OGD/R) reduced neuronal injury in vitro. There were six experimental groups: normal, model, resveratrol pretreatment, resveratrol post-treatment, resveratrol OGD-treatment, and resveratrol whole-processing group. We found that resveratrol in a concentration-dependent manner decreased the activity of lactate dehydrogenase (LDH) and increased the activity of superoxide dismutase (SOD). Moreover, resveratrol, administrated at different times, increased neuronal viability, reduced neuronal apoptosis, upregulated the protein expressions of Nuclear factor erythroid 2-related factor 2 (Nrf-2), NAD(P)H: quinone oxidoreductase 1 (NQO-1), heme oxygenase 1 (HO-1), and Bcl-2, downregulated the protein expression of Caspase-3, and promoted Nrf-2 to transfer into the nuclei from the cytoplasm. The most effective treatment group was the whole-processing treatment group. These results suggest that resveratrol treatment at different times increased neuronal viability and inhibited neuronal apoptosis in vitro, at least in part, via enhancing the activation of the Nrf-2 signaling pathway.

摘要

最近的研究表明,白藜芦醇对脑缺血/再灌注损伤具有保护作用。然而,急性缺血性脑卒中后白藜芦醇治疗的最佳治疗时间尚不清楚。我们旨在研究神经元氧葡萄糖剥夺/复氧(OGD/R)后不同时间给予白藜芦醇是否会减轻体外神经元损伤。有六个实验组:正常组、模型组、白藜芦醇预处理组、白藜芦醇后处理组、白藜芦醇 OGD 处理组和白藜芦醇全程处理组。我们发现白藜芦醇呈浓度依赖性降低乳酸脱氢酶(LDH)的活性,增加超氧化物歧化酶(SOD)的活性。此外,不同时间给予的白藜芦醇可提高神经元活力,减少神经元凋亡,上调核因子红细胞 2 相关因子 2(Nrf-2)、NAD(P)H:醌氧化还原酶 1(NQO-1)、血红素加氧酶 1(HO-1)和 Bcl-2 的蛋白表达,下调 Caspase-3 的蛋白表达,并促进 Nrf-2 从细胞质转位入核。最有效的治疗组是全程处理组。这些结果表明,白藜芦醇在不同时间点的治疗可增加体外神经元活力并抑制神经元凋亡,至少部分是通过增强 Nrf-2 信号通路的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e146/6300780/2deffc3aa07f/10.1177_0963689718780930-fig1.jpg

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