氯胺酮和硝苯吡啶对培养神经元谷氨酸兴奋毒性的保护作用

KETAMINE AND NIFEDIPINE PKOTECT CULTUKED CORTICAL NEUKONS AGAINST INJURIOUS EFFECT OF GTUTAMATE

以体外培养的大鼠胚胎皮层神经元为对象，以培养上清液中乳酸脱氢酶活性为指标，研究了谷氨酸兴奋毒性及药物的保护作用。结果表明，培养１０ｄ的皮层神经元置于含１０或５０μｍｏｌ·Ｌ－１谷氨酸和低糖（１ｇ·Ｌ－１）的ＤＭＥＭ培养液中后，随着作用时间的延长，ＬＤＨ漏出逐渐增加。在谷氨酸处理前，于培养液中加入氯胺酮或硝苯吡啶，则ＬＤＨ漏出量明显低于对照组。氯胺酮和硝苯吡啶并用，ＬＤＨ漏出量比单独使用氯胺酮或硝苯吡啶下降更加明显。结果表明，谷氨酸对培养的神经元可产生严重损伤。氯胺酮和硝苯吡啶单用或并用均有明显的保护作用。

The effects ofglutamate on cultured cortical neurons and the protective effect ofketamine and nifedipine were studied.On day 10 after plating of the cortical cells from 16～18 day-old fetal rats,the cultures were exposed to 50μmol·L-1 glutamate and low glucose(1g·L-1)for 10min～24 h.The results showed that a release of lactate dehydrogenase(LDH)into the culturesupernatant was observed as a function of time.The values of LDH efflux in culture medium wassignificantly lower than those of controls when the cells were pretreated with ketamine or nifedipine 10min prior to addition of glutamate.More significant decrease of LDH activity in culture medium wasobserved when the two drugs were used in combination. These results demonstrate that the dissociatedcuItured cort ical neurons from fetal rat are seriously damaged by glutamate.Such damage could beattenuated by ketamine and nifedipine,suggesting that ketamine and nifedipine may protect neuronsfrom the glutamate toxicity,and the effect of combining ketamine and nifedipine was greater thaneither ketamine or nifedipine alone.