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白藜芦醇对视神经横断后视网膜神经节细胞的神经保护作用。

The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection.

作者信息

Kim Seok Hwan, Park Joo Hyun, Kim Yu Jeong, Park Ki Ho

机构信息

Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Mol Vis. 2013 Jul 25;19:1667-76. Print 2013.

PMID:23901250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3724955/
Abstract

PURPOSE

This study aimed to investigate the neuroprotective effect of resveratrol in an optic nerve transection (ONT) model and to identify the neuroprotective mechanism of resveratrol in retinal ganglion cells (RGCs).

METHODS

ONT and retrograde labeling were performed in Sprague-Dawley rats. Various concentrations of resveratrol were injected intravitreally immediately after ONT. The number of labeled RGCs was determined at 1 and 2 weeks after ONT. The effect of resveratrol and sirtinol (a sirtuin 1 inhibitor) co-injection was investigated. RGC-5 cells were cultured and treated with staurosporine to induce differentiation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the effect of resveratrol on RGC-5 cell survival under serum-free conditions. RGC-5 cells were cultured with sirtinol to investigate the neuroprotective mechanism of resveratrol.

RESULTS

A dose-response relationship was observed between resveratrol and RGC survival. A single intravitreal injection of resveratrol was neuroprotective in RGCs at 1 week after ONT (p<0.01). Repeated intravitreal injection of resveratrol showed a neuroprotective effect at 2 weeks after ONT (p<0.01). However, co-injection of resveratrol and sirtinol diminished the neuroprotective effect of resveratrol (p<0.05). The neuroprotective effect of resveratrol was observed in RGC-5 cells under serum-free conditions, and sirtinol diminished this neuroprotective effect.

CONCLUSIONS

Resveratrol exerts its neuroprotective effect on RGCs via activation of the sirtuin 1 pathway in an ONT model. This finding demonstrates the therapeutic potential of resveratrol in treating optic nerve diseases.

摘要

目的

本研究旨在探讨白藜芦醇在视神经横断（ONT）模型中的神经保护作用，并确定其对视网膜神经节细胞（RGCs）的神经保护机制。

方法

在Sprague-Dawley大鼠中进行ONT和逆行标记。ONT后立即玻璃体内注射不同浓度的白藜芦醇。在ONT后1周和2周测定标记的RGCs数量。研究了白藜芦醇与sirtinol（一种沉默调节蛋白1抑制剂）联合注射的效果。培养RGC-5细胞并用星形孢菌素处理以诱导分化。进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定以评估白藜芦醇在无血清条件下对RGC-5细胞存活的影响。用sirtinol培养RGC-5细胞以研究白藜芦醇的神经保护机制。

结果

观察到白藜芦醇与RGC存活之间存在剂量反应关系。单次玻璃体内注射白藜芦醇在ONT后1周对RGCs具有神经保护作用（p<0.01）。重复玻璃体内注射白藜芦醇在ONT后2周显示出神经保护作用（p<0.01）。然而，白藜芦醇与sirtinol联合注射减弱了白藜芦醇的神经保护作用（p<0.05）。在无血清条件下，在RGC-5细胞中观察到白藜芦醇的神经保护作用，而sirtinol减弱了这种神经保护作用。

结论

在ONT模型中，白藜芦醇通过激活沉默调节蛋白1途径对RGCs发挥神经保护作用。这一发现证明了白藜芦醇在治疗视神经疾病方面的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/b530bf90f50d/mv-v19-1667-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/597998abbc04/mv-v19-1667-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/ca58fc7189dc/mv-v19-1667-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/ac4d964a9235/mv-v19-1667-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/b530bf90f50d/mv-v19-1667-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/597998abbc04/mv-v19-1667-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/82ef001dd268/mv-v19-1667-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/be9795704b88/mv-v19-1667-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/a9f6d5cbec1e/mv-v19-1667-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/ca58fc7189dc/mv-v19-1667-f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d57/3724955/b530bf90f50d/mv-v19-1667-f7.jpg

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