中文摘要：

[摘要]目的研究白藜芦醇在缺氧缺糖再灌注损伤不同时间窗对大鼠皮质神经元氧化应激的影响。方法大鼠皮质神经元缺氧缺糖处理150min，随即恢复正常培养24h。实验分为6组，即正常组、模型组、白藜芦醇预处理组（在缺氧缺糖前加入白藜芦醇干预24h）、造模时处理组（从缺氧缺糖开始加入白藜芦醇干预直至再灌注损伤后24h）、造模后处理组（从缺氧缺糖后加入白藜芦醇干预直至再灌注损伤后24h）和全程处理组（从缺氧缺糖前24h开始加入白藜芦醇干预直至再灌注损伤后24h）。倒置显微镜下观察细胞形态，用化学比色法测定神经元超氧化物歧化酶（SOD）活性以及一氧化氮（NO）的含量，免疫荧光检测观察核因子E2相关因子2（Nrf2）的核移位情况，免疫印迹法检测神经元Nrf2、血红素加氧酶1（HO-1）和苯醌氧化还原酶（NQO-1）蛋白表达。结果培养至第6天，神经元立体感及折光性强。与模型组比较，在白藜芦醇全程处理组中，各浓度（10、20、40、60、80μmol／L）白藜芦醇均可升高神经元SOD活性（P〈0．05），降低NO含量（P〈0．05），其中以40μmol／L白藜芦醇作用最佳；在缺氧缺糖再灌注损伤的不同时间窗内给予白藜芦醇干预，均能减轻缺氧缺糖再灌注导致的细胞损伤，促进Nrf2蛋白从细胞质转移到细胞核，上调Nrf2、HO-1和NQ睁1蛋白的表达，其中全程处理组作用最佳，其次为预处理组。结论白藜芦醇对缺氧缺糖再灌注损伤的神经元有剂量依赖性的抗氧化应激作用，而且全程处理组作用最佳，预处理组次之。其机制可能是通过激活Nrf2／抗氧化反应元件（ARE）信号通路进而上调抗氧化蛋白的表达而实现。

英文摘要：

Objective To investigate the effect of resveratrol on oxidative stress of rat primary cortical neurons during different time windows of oxygen-glucose deprivation/reperfusion （OGD/RP） injury. Methods Rat cortical neurons were cultured under oxygen and glucose deprivation for 150 min and returned to normal culture for 24 h. The experiment was divided into 6 groups, including the normal group, model group, pre treatment group （treated with resveratrol for 24 h prior to OGD）, OGD-treatment group （treated with resveratrol during 150 min of OGD and 24 h of reperfusion）, post treatment group（treated with resveratrol during 24 h of reperfusion）, and the whole processing group （treated with resveratrol for 24 h prior to OGD, during 150 min of OGD, and 24 h of reperfusion）. Invert microscope was used to observe cell morphology. Chemical colorimetry was used to detect the activity of superoxide dismutase （SOD） and the content of nitric oxide （NO）. Immunofluorescence was used to detect the nuclear translocation of nuclear factor erythroid 2 related factor 2 （Nrf2）. Western blotting analysis was used reveal the the protein expressions of Nrf2, heme oxygenase-1 （HO-1） and NADP （H）：quinone oxidoreductase-1 （NQO-1）. Results The stereoscopic effect and refraction of neurons were enhanced at the sixth day of culture. Compared with the model group, resveratrol of various concentrations （10, 20, 40, 60 and 80μmol/ID significantly elevated the activity of SOD and decreased NO content in the whole processing group （P〈0.05） , with the effect being the best when at 40 μmol/L. Compared with model group, resveratrol significantly alleviated neuronal OGD/RP injury, promoted translocation of Nrf2 from the cytoplasm into the nuclei, and upregulated Nrf2, HO-1 and NQO-1 protein expression at all stages of OGD/RP injury, with the best effect found in the whole processing group, followed by the pre~treatment group. Conclusion Resveratrol has a dose-dependent anti-oxidative stress effect o