氯胺酮对培养神经元无氧与再灌损伤保护作用机理的研究

STUDIES ON THE MECHANISM OF PROTECTION OF COLTURED NEUROUS BY KETAMINE ANOXIA/REOXYGENATION INDUCED INJURY

采用１６－１８ｄ胎龄的大鼠皮层细胞分离培养，分别观察无氧再灌和谷氨酸对皮层神经元的影响以及氯胺酮的保护作用。结果如下：培养１２ｄ的细胞先置于缺氧环境中５ｈ，再灌０－２４ｈ后，随着无氧再灌时间延长，ＬＤＨ漏出增加。外源性谷氨酸也引起ＬＤＨ的漏出增加。无氧再灌和谷氨酸处理前，于培养液中加入氯胺酮，则ＬＤＨ漏出量均明显低于对照组。结果表明，无氧和再灌及过量谷氨酸均造成皮层神经元严重损伤，氯胺酮对上述损伤皆有明显的保护作用。以上结果说明谷氨酸兴奋毒性与ＮＭＤＡ受体在缺血性脑损伤过程起着至关重要的作用。

The effects of anoxia/reoxygenation (A/R) and glutamate on cultured cortical neurons from 16 to 18 day old fetal rats and the protective effect of ketamine were studied. The 12 day cultures of 12 days were exposed to anoxia(5h) followed by reoxygenation (0-24h). Following progressive A/R, the release of lactate dehydrogenase(LDH)into the bathing medium obviously increased and exogenous glutamate(3h) also markedly increased the release of LDH. When the cultures were pretreated with ketamine before A/R, the amounts of LDH efflux in culture medium were significantly less than those of controls. These results demonstrate that the cultured cortical neurons are seriously damaged by A/R and exogenous glutamate. Such damage could be attenuated by ketamine, suggesting that the neurotoxic effect of glutamate and NMDA (N methyl D aspartate) receptors play an important role in the process of ischemia induced damage in the brain.