大鼠脑损伤后谷氨酸引起乳酸含量变化的作用机制

Mechanism of glutamate-induced lactate changes in rat traumatic brain injury

目的探讨大鼠脑损伤后谷氨酸引起乳酸含量变化的作用机制。方法28只大鼠随机分为对照组、犬尿烯酸(KYN)灌注组、Ouabain灌注组及Ba2+灌注组,每组7只。在建立大鼠局部脑损伤模型前后,应用微透析技术将格林液、KYN、Ouabain和Ba2+分别灌注到各组大鼠致伤脑区,在致伤前45min开始和致伤后90min内,观察3种药物对脑损伤后乳酸含量的影响。结果对照组伤前乳酸含量为(0.28±0.07)mmol/L,脑损伤后引起乳酸含量迅速升高,伤后15min达到峰值(0.75±0.18)mmol/L,乳酸含量持续升高60min后逐渐下降至接近伤前水平。Ouabain灌注组及KYN灌注组伤后乳酸含量升高幅度减弱,持续时间缩短。Ba2+灌注组乳酸含量升高幅度增加,持续时间延长。结论脑损伤后异常增加的谷氨酸作用于兴奋性氨基酸受体偶联离子通道,引起细胞外K+增加,使Na+-K+泵活性增强,继而导致糖酵解代谢水平增高,乳酸含量增加。

Objective To explore the mechanism of glutamate-induced lactate changes in traumatic brain injury rat. Methods Twenty eight traumatic brain injury rats were randomly divided into control group, kynurenic acid （KYN） perfusion group, ouabain perfusion group and barium （Ba^2＋） perfusion group, 7 rats in each group. Ringer solution, KYN, ouabain and Ba^2＋ were perilled into the injured cortex of each group respectively. The changes of brain lactate content were observed by microdialysis technique from 45 minutes before to 90 minutes after the rat model establishment. Results The content of lactate was 0.28 ± 0.07 mmol/L before the brain injury in control group. The value was increased after the brain injury and reached peak value （0.75 ± 0.18 mmol/L） in the first 15 min and lasted to 60 min, then decreased to normal level gradually. The increasing amplitude of lactate was attenuated and the time span was shortened after intervention of ouabain and KYN, however, the increasing amplitude and the time span were all increased in Ba^2＋ perfusion group. Conclusion The mechanism of glutamine-induced lactate changes following brain injury may as follows： the increased glutamate affects the excitatory amino acid-coupled ionic channel, resulting in increasing of K^＋ outside the cell, activating of Na^＋-K^＋ pump, which in turn promote glycolysis and increases lactate level.