拉莫三嗪干预颞叶癫痫发作及其神经保护作用的研究  

Effects of lamotrigine on epileptogenesis and neuroprotection in epileptic rats

作　　者：陈彦军[1] 王琼[1] 闫欣[2] 孙美珍[1] 

机构地区：[1]山西医科大学第一医院神经内科,太原030001 [2]山西医科大学第一医院药物临床研究机构,太原030001

出　　处：《中华脑科疾病与康复杂志（电子版）》2015年第1期23-26,共4页Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）

基　　金：山西省国际科技合作项目(2010081067)

摘　　要：目的探讨在毛果芸香碱诱导颞叶癫痫大鼠模型中,拉莫三嗪(LTG)对癫痫发作的影响和神经保护作用。方法取雌性Wistar大鼠32只,腹腔注射毛果芸香碱直至出现Ⅳ级以上无明显间歇的癫痫持续状态(SE),SE后1 h给地西泮终止发作并存活者为造模成功的大鼠,将其随机分为4组(每组各8只):(1)对照组:用等体积生理盐水取代制作模型的药物与LTG;(2)模型组:用等体积生理盐水取代LTG,2次/d,灌胃;(3)LTG低剂量组:LTG 10 mg/kg,2次/d,灌胃;(4)LTG高剂量组:LTG 20 mg/kg,2次/d,灌胃。各组动物均在SE后24 h开始给药,连续给药10 d。采用视频录像记录大鼠癫痫发作次数,并分析各组间的差异;行Nissl染色和GFAP免疫组化染色观察海马神经元丢失和星形胶质细胞的增生,采用SPSS 17.0统计软件,对各组实验数据进行统计学分析。各组每周每只大鼠发作次数比较、各组大鼠海马CA3区神经元计数比较及各组大鼠海马CA1星形细胞计数比较均采用单因素方差分析和LSD检验,以P<0.05为差异有统计学意义。结果与对照组及模型组比较,LTG用药组大鼠癫痫发作频率、海马神经元丢失和星形胶质细胞增生均明显减少(与对照组比较t值分别为8.334、10.877、-7.460,均P<0.05;与模型组比较t值分别为-4.133、6.520、-8.541,均P<0.05)。与高剂量LTG组比较,低剂量LTG组大鼠癫痫发作频率更高、海马神经元丢失更多和星形胶质细胞增生减少更明显(t值分别为-6.297、5.030、-2.864,均P<0.05)。结论在本大鼠模型中,LTG可减少癫痫发作频率,使海马神经元丢失和星形胶质细胞增生均明显减少,LTG具有抗癫痫发作和神经保护作用。Objective To observe the effects of lamotrigine （ LTG ） on epileptogenesis and neuroprotection in lithium-pilocarpine induced rat model of temporal lobe epilepsy. Methods Thirty-two Wistar female rats were injected with pilocarpine on intraperitoneal way and till appeared epileptic status （SE）of five grades. When the seizure were stoped by diazepam 1 hour after SE, the surviving rats were successful model and were randomly divided into four groups （ eight rats in each group） ： （ 1 ） Control group ： the same volume saline replaced both the drugs used in making the model and LTG ; （2） Model group ： the same volume saline replaced LTG,twice a day to fill the stomach;（3）Low dose LTG group：10 mg/kg LTG, twice a day to fill the stomach;（4）High dose LTG group ：20 mg/kg LTG, twice a day to fill the stomach. All rats were given saline or LTG during 24 h after SE and continued 10 days. The numbers of spontaneous recurrent seizure （SRS） were recorded by digital video. The neuronal loss and gliosis in hippocampus were analyzed by neuronal Nissl staining and immunohistochemical methods of glial fibrillary acidic protein （GFAP）. The software of SPSS 17.0 was used for statistical analysis. The data of the number of SRS, the degree of neuronal loss and gliosis in hippocampus were analyzed by One-Way ANOVA and LSD test. P 〈0. 05 was considered statistical differences. Results Compared with control group and model group, the numbers of SRS and the neuronal loss, gliosis in hippocampus were decreased by LTG significantly （ control group t values were 8. 334, 10. 877, -7. 460, respectively, all P 〈 0. 05; model group t values were -4. 133,6. 520, -8. 541 ,all P 〈 0. 05）. High dose LTG group decreased the numbers of SRS, the neuronal loss and gliosis significantly compared with low dose LTG group （ t values were - 6. 297,5. 030, - 2. 864, respectively, all P 〈 0. 05 ）. Conclusion Lamotrigine may prevent epileptogenesis and has neuroprotection effects in model of temporal l

关 键 词：癫痫 癫痫 强直阵挛性 毛果芸香碱 神经保护 拉莫三嗪 

分 类 号：R742.1[医药卫生—神经病学与精神病学]