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抗痫促智药物对认知功能障碍致痫大鼠海马细胞外信号调节激酶2及神经细胞黏附分子1表达的影响 被引量:7

Effect of anti-epileptic, nootropic drugs on the expression of ERK2 and NCAM1 in the hippocampus chan- ges on the epileptic rats with cognitive dysfunction
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摘要 目的 探讨细胞外信号调节激酶2(ERK2)及神经细胞黏附分子1(NCAM1)在癫痫认知功能障碍中的作用及抗痫、促智药物对二者作用.方法 将120只Wistar大鼠分为对照组、致痫组和卡马西平组、奥卡西平组、茴拉西坦组、盐酸多奈哌齐组治疗30 d,对照组用生理盐水造模,其余5组用匹罗卡品诱导癫痫模型,将造模成功的大鼠给予上述成药物干预模型,大鼠的学习记忆能力通过Morris水迷宫实验测试,记录逃避潜伏期和原平台象限游泳时间;并用RT-PCR法检测NCAM1、ERK2在大鼠海马组织中的mRNA表达,免疫组化法检测大鼠海马组织中NCAM1和ERK2的蛋白表达.结果 定位航行试验中,与对照组大鼠逃避潜伏期相比,致痫组[(67.14±7.37)s]>对照组[(35.78±4.84)s](P<0.01),其中卡马西平组与盐酸多奈哌齐组与致痫组比较,卡马西平组[(81.23±9.46)s]>致痫组[(67.14±7.37)s](P<0.01),盐酸多奈哌齐组[(53.75±6.74)s]<致痫组[(67.14±7.37)s](P<0.01).各组ERK2蛋白表达及mRNA比较为:卡马西平组<奥卡西平组<致痫组<茴拉西坦组<多奈哌齐组<对照组.与对照组比,多奈哌齐组>对照组(P<0.01),茴拉西坦组>对照组(P<0.05).结论 ERK2在癫痫发作30 d时在海马的表达水平下降,NCAM1则相反,ERK2活性的减低和NCAM1的过度表达可能是癫痫后认知功能损害的潜在机制.卡马西平能加重癫痫认知功能障碍程度,盐酸多奈哌齐可明显改善癫痫鼠的认知功能. Objective To study the effect of anti-epileptic,nootropic drugs on the expression of NCAM and ERK2 in the hippocampus changes on the epileptic rats with cognitive dysfunction.Methods A total of 120Wistar rats were used.20 controls and 100 in which epilepticus with cognitive dysfunction were randomly assigned to 5 groups (n =20/group) that received daily treatments for 30 days with either (1) saline (epilepsy),(2) carbamazine (traditional anti-epileptic),(3) oxcarbazine (new anti-epileptic),(4) aniracetam (brain protective),or (5) donepezil (nootopic).Spatial learning and memory were assessed with a Morris Water Maze (MWM).Hippocampus tissue was assessed for NCAM1 and ERK-2 mRNAs by RT-PCR and proteins by immunochemistry.Results The mean escape latency of the place navigation test:EP group ((67.14 ± 7.37)s)was all higher than NS group (35.78 ± 4.84 s)and there was statistical significance (P 〈 0.01),carbamazepine group ((81.23 ± 9.46)s) 〉 EP group((67.14 ±7.37)s) 〉 donepezi group((53.75 ±6.74) s) (P〈0.01).Immunohistochemical and RT-PCR result:carbamazepine 〈 oxcarbazepine 〈 epilepsy 〈 aniracetam 〈 donepezi group.Compared with control group,donepezil group 〉 control group (P 〈 0.01),aniracetam group 〉 control group (P 〈 0.05).Conclusion ERK-2 expression is decreased and NCAM 1 expression is increased in the hippocampus in the epileptic rats.Thus,both are involved in cognitive dysfunction.Carbamazepine aggravates cognitive dysfunction,whereas donepezil improves cognitive dysfunction associated with epilepsy.
出处 《中华行为医学与脑科学杂志》 CAS CSCD 北大核心 2013年第8期696-699,共4页 Chinese Journal of Behavioral Medicine and Brain Science
基金 山东省自然科学基金资助项目(2009ZRB02602)
关键词 癫痫 神经细胞黏附分子1 细胞外信号调节激酶2 认知功能障碍 Epilepsy NCAM1 ERK2 Cognitive dysfunction
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