氯胺酮对缺氧复氧诱导胎鼠大脑皮层神经细胞谷氨酸释放的影响

Effects of ketamine on anoxia-reoxygenation induced glutamate release from cerebral cortex neurons of fetal rats

目的观察氯胺酮对缺氧复氧诱导胎鼠大脑皮层神经细胞谷氨酸释放的影响。方法胎龄16～18d Wistar大鼠的大脑皮层神经细胞,行原代培养,培养的神经细胞随机分为3组,对照组不进行缺氧处理(n=6),缺氧复氧组行缺氧5h复氧(n=6)及氯胺酮组。氯胺酮组随机分为K_1、K_(20)、K_(100)亚组(n=6),均行缺氧5h复氧,K_1、K_(20)、K_(100)组于缺氧前即刻分别予以氯胺酮1、20、100μmol/L终浓度处理。各组于复氧24h时采用高效液相色谱法测定培养液谷氨酸浓度。结果缺氧复氧可导致谷氨酸浓度升高；20、100μmol/L氯胺酮可抑制神经细胞谷氨酸释放,且浓度越高,抑制程度越大。结论氯胺酮可抑制缺氧复氧诱导的胎鼠大脑皮层神经细胞谷氨酸的释放,呈剂量依赖性。

Objective To investigate the effects of ketamine on anoxia-reoxygenation （A/R） induced glutamate release from cerebral cortex neurons. Methods Primary, cultured neurons obtained froln cerebral cortex of fetal Wistar rats （16-18 d） were randomly divided into 3 groups： i control group; Ⅱ A/R group and m ketamine pretreatment ＋ I/R group. The control group was not subjected to A/R while A/R group was exposed to anoxic air （95% N2 ＋ 5% CO2） for 5 h followed by 24 h reoxygenation, in group m different doses of ketamine were added to the cuhure media before anoxia and the final ketamine concentrations were l, 20 and 100 μmol·L^-1 respectively. The extracellular glutamate concentration was detected at the end of 24 h reoxygenation. Results The extracellular glutamate concentration was significantly higher after 24 h reoxygenation in A/R group than in control group, Ketamine 20 and 100 μmol·L^-1 significantly inhibited glutamate release from the neurons induced by A/R in a dose-dependent manner. Conclusion Ketamine can inhibit glutamate release from neurons induced by A/R in a dose-dependent manner.