氯胺酮对胎鼠大脑皮层神经元缺氧复氧损伤时一氧化氮的影响

Effect of Ketamine on Nitric Oxide Released from Cerebral Cortex Neurons of Fetal Rats In-duced by Anox!a-reoxygenation

【目的】了解氯胺酮对神经元缺氧复氧损伤时的保护作用和机制。【方法】应用无血清原代培养的胎鼠大脑皮层神经元，进行缺氧结合无糖处理。对照组及缺氧组分别于缺氧即刻和复氧不同时间取培养上清液测定N0浓度；并将缺氧1h组细胞于缺氧处理开始时分别给予1、20、100μmol／L氯胺酮，于缺氧后复氧24h测定细胞外液NO浓度。【结果】缺氧后N0浓度随复氧时间的延长而增加，至24h达高峰，且随缺氧时间的延长，N0浓度逐渐增加，与对照组相比（P〈0．01），至缺氧5hN0浓度达高峰。对于缺氧1h组，缺氧开始时给予不同浓度的氯胺酮预处理后，各组细胞外液NO浓度逐渐降低，呈现明显的剂量依赖性，与缺氧组比较均有差异（P〈0．05），至氯胺酮100μmol／L时恢复至接近对照组水平（P〉0．05）。【结论】N0与脑皮层神经元缺氧复氧损伤的发生密切相关，氯胺酮可通过调控N0生成量或阻断其合成通路，发挥神经元保护作用。

[Objective] To understand the protective effects of ketamine on neuron in anoxia-reoxygenation injury and its mechanism. [Methods]The primary cultured cerebral cortex neurons in embryonic rat were deprived of both oxygen and glucose. The supernatant liquid in control group and anoxic group were obtained at immediate time of anoxia and different time of reoxygenation to detect the level of nitric oxide（NO）. The 1- hour anoxia group was given 1, 20 and 100μmol/L ketamine at the beginning of anoxia, respectively. NO level in extracellutar fluid was measured at 24h after anoxia-reoxygenation. [Results] NO level after anoxia in- creased as the time went up, and reached the peak at 24h. As the time of anoxia went up, NO level increased gradually compared with the control group（ P〈0.01）, and reached the peak at 5h. In 1-hour anoxia group, the extracellular concentration of NO gradually decreased in a dose-dependent manner after the administration of different concentration of ketamine at the beginning of anoxia, and there was significant difference between 1-hour anoxia group and anoxia group（ P 〈0.05）. When ketamine was 100μmol/L, NO concentration closed to the level of the control group（ P 〉0.05）. [Conclusion] NO is closely correlated with the genesis of anoxiareoxygenation injury of cerebral cortex. Ketamine has the protective effect on neuron through regulating the production of NO or blocking its synthesis path.