Resveratrol inhibits oligomeric Aβ-induced microglial activation via NADPH oxidase
Resveratrol inhibits oligomeric Aβ-induced microglial activation via NADPH oxidase
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DOI：
10.3892/mmr.2015.4199
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发表时间：
2015-10-01
影响因子：
3.4
通讯作者：
Li, Wei-Qi
中科院分区：
文献类型：
--
作者：
Yao, Yao;Li, Juan;Li, Wei-Qi
小胶质细胞介导的神经炎症是阿尔茨海默病（AD）发病机制的关键。一些研究表明，NADPH氧化酶有助于小胶质细胞介导的神经炎症。白藜芦醇是一种天然多酚类化合物，由于其抗炎特性，在AD中发挥神经保护作用。本研究旨在研究白藜芦醇对寡聚淀粉样蛋白β（oA β）诱导的BV-2小胶质细胞活化的影响，并确定NADPH氧化酶在这些影响中的作用。通过高含量筛选细胞计数和使用溴脱氧尿苷掺入测定来测量小胶质细胞增殖。此外，还评估了活性氧（ROS）、一氧化氮（NO）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1 β的水平。本研究的结果表明，白藜芦醇抑制oA β诱导的小胶质细胞的增殖和促炎因子，包括ROS，NO，TNF-α和IL-1 β的产生。随后的机制研究表明，白藜芦醇抑制oA β诱导的p47 phox和gp 9 lphox的mRNA和蛋白表达水平。这些结果表明，NADPH氧化酶可能是一个潜在的治疗AD的目标，白藜芦醇可能是一个有价值的天然产物，具有治疗AD的潜力。
Microglia-mediated neuroinflammation is key in the pathogenesis of Alzheimer's disease (AD). Several studies have suggested that NADPH oxidase contributes to microglia-mediated neuroinflammation. Resveratrol, which is a natural polyphenolic compound, exerts neuroprotective effects in AD due to its anti-inflammatory properties. The present study aimed to investigate the effects of resveratrol on the activation of oligomeric amyloid beta (oA beta)-induced BV-2 microglia, and to determine the role of NADPH oxidase in these effects. Microglial proliferation was measured by high-content screening cell counting and using a bromodeoxyuridine incorporation assay. In addition, the levels of reactive oxygen species (ROS), nitric oxide (NO), tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta were assessed. The results of the present study demonstrated that resveratrol inhibited the proliferation of oA beta-induced microglia and the production of pro-inflammatory factors, including ROS, NO, TNF-alpha and IL-1 beta. Subsequent mechanistic investigations demonstrated that resveratrol inhibited the oA beta-induced mRNA and protein expression levels of p47phox and gp9lphox. These results suggested that NADPH oxidase may be a potential target for AD treatment, and resveratrol may be a valuable natural product possessing therapeutic potential against AD.