活性氧参与-氧化氮诱导的神经细胞凋亡

采用激光共聚焦成像技术，用氧化还原敏感的特异性荧光探针(DCFH-DA和DHR123)直接研究了一氧化氮供体S-亚硝基-N-乙酰基青霉胺(SNAP)诱导未成熟大鼠小脑颗粒神经元凋亡过程中的细胞胞浆、线粒体中活性氧水平的变化，发现神经细胞经0.5mmol/LSNAP处理1h后，细胞胞浆及线粒体中活性氧水平大大增加.一氧化氮清除剂血红蛋白能够有效抑制细胞胞浆、线粒体中活性氧的产生，防止细胞凋亡.外源性谷胱甘肽对细胞也具有良好的保护作用，而当细胞中谷胱甘肽的合成被抑制后，一氧化氮的神经毒性大大增强.实验结果表明一氧化氮通过促进神经细胞产生内源性活性氧而启动细胞凋亡程序，而谷胱甘肽可能是重要的防止一氧化氮引发神经损伤的内源性抗氧化剂

Reactive Oxygen Speciesare Involved in Nitric Oxide-InducedApoptosis of Neurons

With redox-sensitive fluorescene probes DCFH-DA and DHR123, the formation of cytosolic andintramitochondrial reactive oxygen species (ROS) inside immature rat cerebellar granule cells during theapoptosis induced by nitric oxide donor S-nitroso-N-acetyl-pennicillamine (SNAP) was monitored by laserconfocal scanning microscopy. The cytosolic and intramitochondrial ROS increase significantly after 0.5 mmol/LSNAP treatment for 1 h. Pre-treatment with the nitric oxide scavenger hemoglobin can effectively inhibit theformation of cytosolic and intrarnitochondrial ROS and protect neurons from apoptosis. Adding glutathione canalso protect neurons from apoptosis, and the cytotoxity of nitric oxide increases significantly while the synthesisof glutathione is inhibited. The results indicated that ROS might be involved in NO-induced apoptosis in neuralcells and glutathione might be the endogenesis antioxidant to protect neurons from oxidative injury.