摘要
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 rat model of lithium-pilocarpine-induced epilepsy （LPE）. Methods of intravenous oxaloacetate （OxAc） in a Thirty 6 - 8 weeks old male Sprague- Dawley rats, weighing 180 - 220 g, were randomly divided into control group, LPE model group, LPE ＋ OxAc group, LPE ＋ OxAc ＋ glutamate-oxaloacetate transminase （GOT） group, and LPE ＋ OxAc ＋ maleate group, 6 in each group. Rats in control group were given saline instead of pilocapine, rats in LPE model group and LPE ＋ OxAc group were injected with OxAc at the dose of 3.5 mg/100 g when the seizure of epilepsy was arres- ted, rats in LPE ＋ OxAc ＋ GOT group were injected with OxAc at the dose of 3.5 mg/100 g and GOT at the dose of 3.5 μg/100 g when the seizure of epilepsy was arrested, and rats in LPE ＋ OxAc ＋ maleate group were injected with OxAc at tile dose of 3.5 mg/100 g and maleate at the dose of 6.3mg/100 g when the seizure of epilepsy was arrested. Sixty minutes after a rat epilepsy model was induced with lithium-pilocarpine, seizure of epilepsy was arrested by injecting diazepam. Glutamate level in cerebrospinal fluid and blood was measured, findings on electroencephalogram（EEG） and neuronal loss in different experimental groups were recorded at dif- ferent time points. Results The level of glutamate in cerebrospinal fluid and blood was about 88% and 54% higher in LPE model group than in control group after the seizure of epilepsy was arrested （ P 〈 0.05 ） andreached its peak at 8 h, th duce the glutamate level in rested （P 〈 0. 05）. OxAc en began to decrease slowly, indicating that intravenous OxAc could significantly re- cerebrospinal fluid and blood within 8 and 12 h after the seizure of epilepsy was ar- could also significantly improve the EEG and neuronal loss in hippcampus and den- tate hilus. Intravenous GOT could improve the neuroprotective effect of OxAc, while maleate （ a specific inhibi- tor of GOT） could attenuate the neuroprotective effect of OxAc in rats
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2012年第14期1375-1379,共5页
Journal of Third Military Medical University
基金
国家自然科学基金(84402511
81072706)
重庆市教育委员会科学技术研究项目(KJ090306)
重庆市自然科学基金(CSTC2011jjA10004)~~
关键词
草酰乙酸
谷氨酸
谷草转氨酶
癫痫
oxaloacetate
glutamic acid
glutamate-oxaloacetate transaminase
epilepsy
