Quercetin Enhances Exercise-Mediated Neuroprotective Effects in Brain Ischemic Rats
Quercetin Enhances Exercise-Mediated Neuroprotective Effects in Brain Ischemic Rats
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DOI：
10.1249/mss.0000000000000310
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发表时间：
2014-10-01
期刊：
影响因子：
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通讯作者：
Wang, Ray-Yau
中科院分区：
文献类型：
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作者：
Chang, Heng-Chih;Yang, Yea-Ru;Wang, Ray-Yau
目的：脑缺血后氧自由基明显增加，在脑缺血再灌注损伤机制中起重要作用。调节脑缺血后的氧化应激反应提供了一种潜在的治疗策略。槲皮素是一种天然类黄酮，具有抗氧化特性。然而，它保护细胞的机制还不完全清楚。运动训练还可以减少氧化应激，促进大脑恢复。本研究的目的是确定运动训练和槲皮素联合治疗是否能对脑缺血大鼠产生更好的神经保护和功能恢复。方法：将大鼠随机分为：大脑中动脉阻塞(MCAO)+安静对照组、MCAO+槲皮素组、MCAO+运动组和MCAO+运动组。为探讨PI3K/Akt通路在Qetetin和运动介导的神经保护中的作用，本研究增加了两组：MCAO+Quercetin+PI3K/Akt抑制剂组(LY294002)和MCAO+运动+Qetetin+PI3K/Akt抑制剂组。在MCAO后24小时和14天进行运动功能检查。脑组织样本被用来测量抗氧化和抗凋亡蛋白的表达，以及测量脑梗塞体积。结果：运动或槲皮素治疗显著减少氧化应激和脑梗塞体积，增加抗氧化和抗凋亡信号，并改善运动功能。运动训练和槲皮素联合治疗比单独使用任何一种治疗效果更好。抑制PI3K/Akt可消除运动训练和Qetetin处理的保护作用。结论：Quercetin通过上调PI3K/Akt活性促进抗氧化和抗凋亡信号转导，从而促进脑缺血后运动介导的功能恢复。
Purpose: Reactive oxygen species are markedly increased after ischemia and play important roles in the mechanism of ischemia-reperfusion injury. Regulating the oxidative stress response after brain ischemia provides a potential therapeutic strategy. Quercetin is a natural flavonoid that exhibits antioxidant properties. However, the mechanisms by which it protects cells are not fully understood. Exercise training also reduces oxidative stress and enhances brain recovery. The purpose of this study was to determine whether combined exercise training with quercetin treatment could result in better neuroprotection and functional recovery in rats subjected to brain ischemia. Methods: Rats were randomly assigned to the following groups: middle cerebral artery occlusion (MCAO) with rest control, MCAO with quercetin, MCAO with exercise, or MCAO with exercise and quercetin. To determine the effect of PI3K/Akt pathway in quercetin and exercise-mediated neuroprotection, two additional groups, a group of MCAO with quercetin and PI3K/Akt inhibitor (LY294002) and a group of MCAO with exercise, quercetin, and PI3K/Akt inhibitor, were added in this study. Motor function was examined at the 24th hour and 14th day post-MCAO. Brain samples were used to measure the expression of antioxidative and antiapoptotic proteins as well as to measure the infarct volume. Results: Treatment with either exercise or quercetin significantly decreased oxidative stress and infarct volume, increased antioxidative and antiapoptotic signaling, and improved motor function. Exercise training combined with quercetin treatment resulted in better outcomes than either treatment alone. PI3K/Akt inhibition eliminated the protective effects of exercise training and quercetin treatment. Conclusion: Quercetin enhances exercise-mediated functional recovery after brain ischemia via up-regulation of PI3K/Akt activity to promote antioxidative and antiapoptotic signaling.