奥卡西平和卡马西平对致（痫）大鼠认知功能的影响

The influence of oxcarbazepine and carbamazepine on cognitive function of epileptic rats

目的 观察卡马西平、奥卡西平对癫（痫）认知功能的影响.方法 采用随机数字表方法将实验大鼠分为对照组、致（痫）组、奥卡西平组及卡马西平组,每组各20只.对照组用0.9％氯化钠注射液造模;致（痫）组用氯化锂-匹罗卡品造模,不服用药物;奥卡西平组用氯化锂-匹罗卡品造模,并用奥卡西平200 mg/d灌胃;卡马西平组用氯化锂-匹罗卡品造模,并用卡马西平200 mg/d灌胃,通过Morris水迷宫实验测试并记录逃避潜伏期和平台象限游泳时间.实时聚合酶链反应（RT-PCR）法检测ERK-2 mRNA、NCAM-1 mRNA表达,免疫组织化学化法检测细胞外调节蛋白激酶2 （ERK-2）蛋白、神经细胞黏附分子1（NCAM-1）蛋白表达（阳性神经元计数）.结果 训练初期,卡马西平组、奥卡西平组、致（痫）组、对照组逃逸潜伏期平均时间、平台象限游泳时间分别为（81±9）和（27±9）s,（72 ±9）s和（32±14）s,（67 ±7）s和（37±13）,（36±5）s和（51 ±11）s,卡马西平组、奥卡西平组、致（痫）组和对照组比较,差异均有统计学意义（均P＜0.01）.卡马西平组、奥卡西平组、致（痫）组、对照组NCAM/β3-actin和ERK-2 /β3-actin分别为0.60±0.12和0.43 ±0.11、0.66 ±0.03和0.51±0.17、0.95 ±0.21和0.59±0.24、0.48±0.04和0.75 ±0.23,卡马西平组、奥卡西平组的大鼠海马组织NCAM-1 mRNA表达水平明显低于致（痫）组（P＜0.01）.致（痫）组中ERK-2的mRNA表达水平明显低于对照组（P＜0.01）.卡马西平组、奥卡西平组的大鼠海马组织中ERK-2表达水平明显低于致（痫）组（P＜0.01）.结论 ERK-2在癫（痫）发作1个月时在海马的表达水平下降,NCAM-1则相反.二者均参与了癫（痫）认知功能障碍的发病,卡马西平能加重癫（痫）认知功能障碍,奥卡西平对癫（痫）认知功能障碍影响轻微.

Objective To study the expression changes of neural celladhesion molecule 1 （NCAM 1） and extracellular signalregulated kinases 2 （ERK-2） in a rat model of epilepsy＇hippocampus with cognitive dysfunction.Methods Male Wistar rats were randomly divided into control group,epilepsy group,carbamazepine group and oxcarbazepine group（20 cases in each group）.In expermental group,lithium chloride and methylscopolamine were uesd to build the rat model of epilepsy.The control model group had saline.The carbamazepine and oxcarbazepine were respective used in different groups as treatment（i.g,200mg/d per rat）.The learning and memory ability was observed.The Hippocampus was dissected one day after this text.RT-PCR was used to detect the mRNA expression of NCAM-1 and ERK-2.ELISA was used to detect the protein expression of NCAM 1and ERK-2.Results The results of mean escape latency of Morris water maze test showed that carbamazepine group was （81 ±9）s and （27 ±9）s ;oxcarbazepine group was （72 ±9）s and （32 ± 14） s;epilepsy group was （67 ±7）s and （37 ± 13）s;control group was （36 ±5）s and （51 ± 11）s（P ＜0.01） The expression level of NCAM/β-actin and ERK-2/β3-actin was 0.60 ± 0.12 and 0.43 ± 0.11 （carbamazepine group） ; 0.66 ± 0.03 and 0.51 ± 0.17 （oxcarbazepine group） ;0.95 ± 0.21 and 0.59 ± 0.24 （epilepsy group） ; 0.48 ± 0.04 and 0.75 ± 0.23 （control group）.The gene expression level of NCAM-1 was lower in the treatment group compared with that in epilepsy group（P ＜0.01）.The expression level of ERK-2 was lower in the treatment groups compared with that in the epilepsy group.Conclusions The expression of ERK-2 in the hippocampus was decreased and NCAM-1 was increased at 1 month.The results showed thatboth carbamazepine and oxcarbazepin participated in the pathogenesy of cognitive dysfunctionof epilepsy.Carbamazepine can aggratate the cognitive dysfunction.