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目的观察静脉注射草酰乙酸(oxaloacetate,OxAc)对氯化锂-匹罗卡品癫痫(lithium-pilocarpine seizures,LPS)模型大鼠的神经保护作用。方法 30只6～8周龄、体质量180～220 g的Sprague-Dawley雄性大鼠按随机数字表法分为5组:生理盐水对照组(用0.9%生理盐水代替匹罗卡品)、LPS模型对照组、LPS+OxAc组(癫痫持续状态终止时注射OxAc 3.5 mg/100 g)、LPS+OxAc+谷草转氨酶(glutamate-oxaloacetate transminase,GOT)组(癫痫持续状态终止时注射OxAc 3.5 mg/100 g+GOT 3.5μg/100 g)及LPS+OxAc+马来酸盐(Maleate)组(癫痫持续状态终止时注射OxAc3.5 mg/100 g+Maleate 6.3 mg/100 g)(n=6)。用氯化锂和匹罗卡品制备癫痫动物模型,诱发癫痫持续状态(status epi-lepticus,SE)60 min后注射安定终止发作。分别检测SE终止后不同时间点各实验组大鼠脑脊液与血液中的谷氨酸浓度、脑电图表现及神经元脱失情况。结果 LPS模型对照组大鼠SE终止后脑脊液与血液中的谷氨酸浓度显著升高,8 h左右达到最高峰,与生理盐水对照组相比,分别升高了约88%和54%,随后开始缓慢下降。在SE终止后静脉注射OxAc可以在8 h内明显降低癫痫大鼠脑脊液中的谷氨酸浓度(P<0.05),8 h后其作用基本消失;OxAc对癫痫大鼠血液中谷氨酸浓度的降低作用可以持续至注射后12 h(P<0.05)。OxAc对癫痫大鼠脑电图表现及海马、齿状回门区神经元脱失现象也有明显改善作用。在应用OxAc的同时,静脉注射GOT可以增强OxAc对LPS大鼠的神经保护作用,而同时应用GOT特异性抑制剂Maleate可以减弱OxAc的上述作用效果。结论静脉注射OxAc可通过促使血液中谷氨酸浓度下降而对氯化锂-匹罗卡品癫痫模型大鼠的神经起到保护作用。
Objective To observe the neuroprotective effect of intravenous oxaloacetate (OxAc) on lithium-pilocarpine seizures (LPS) model rats. Methods Thirty male Sprague-Dawley rats aged 6-8 weeks and weighing 180-220 g were randomly divided into 5 groups: saline control group (0.9% saline instead of pilocarpine), LPS The rats in the model control group, LPS + OxAc group (OxAc 3.5 mg / 100 g at the end of status epilepticus) and LPS + OxAc + glutamate-transaminase group + GOT 3.5 μg / 100 g) and LPS + OxAc + maleate group (OxAc 3.5 mg / 100 g + Maleate 6.3 mg / 100 g at the end of status epilepticus) (n = 6). Animal models of epilepsy were prepared with lithium chloride and pilocarpine, and seizure was stopped 60 minutes after status epi-lepticus (SE) was induced. The levels of glutamate, EEG and neuron loss in cerebrospinal fluid and blood of rats in each experimental group were detected at different time points after SE termination. Results The concentrations of glutamic acid in cerebrospinal fluid and blood were significantly increased in the LPS model control group after SE termination and reached its peak at about 8 h, which were increased by about 88% and 54% respectively compared with the saline control group Start slowly down. Intravenous injection of OxAc at the end of SE significantly reduced glutamate concentration in the cerebrospinal fluid of epileptic rats within 8 h (P <0.05), and disappeared after 8 h. OxAc decreased the concentration of glutamic acid in the blood of epileptic rats The effect lasted 12 h after injection (P <0.05). OxAc on epilepsy rats EEG performance and hippocampus, dentate gyrus neuron loss phenomenon also significantly improved. In the application of OxAc, intravenous injection of GOT can enhance the neuroprotective effects of OxAc on LPS rats, while the use of GATE-specific inhibitor Maleate can reduce the above effects of OxAc. Conclusion Intravenous injection of OxAc can protect the nerves of rats induced by lithium chloride-pilocarpine epilepsy by decreasing the concentration of glutamate in the blood.