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目的 探讨左乙拉西坦对癫痫幼鼠学习记忆能力的影响.方法 将96只清洁级Wistar雄性幼鼠随机分为4组,对照组正常饲养,其余3组制备癫痫模型;模型制备成功后,左乙拉西坦干预组(Lev干预组)和阳性药卡马西平干预组(Car干预组)分别采用左乙拉西坦和卡马西平混悬液灌胃,持续4周.采用矿场实验和水迷宫实验评估其学习记忆能力;采用ELISA实验测定海马组织5-羟色胺(5-HT)含量;采用多聚甲醛心脏灌注实验和免疫荧光实验测定海马组织5-HT受体5-HTR1A、5-HTR2C 、5-HTR3A表达水平.结果 经3次癫痫诱发实验可获得稳定癫痫模型,癫痫级别为5~7级.与对照组相比,其余各组矿场穿越方格数、穿过平台数和平台停留时间减少,定位导航时间延长;与模型组相比,Lev和Car干预组矿场穿越方格数、穿过平台数和平台停留时间增加,定位导航时间缩短;与Lev干预组相比,Car干预组矿场穿越方格数和平台停留时间减少,定位导航时间延长;组间比较差异有统计学意义(均P<0.05).与对照组相比,其余各组5-HT含量和5-HTR1A、5-HTR2C表达水平降低,5-HTR3A表达水平升高;与模型组相比,Lev和Car干预组海马组织5-HT含量和5-HTR1A、5-HTR2C表达水平升高,5-HTR3A表达水平降低;与Lev干预组相比,Car干预组海马组织5-HTR1A表达水平降低,5-HTR3A表达水平升高;组间比较差异有统计学意义(均P<0.05).结论 左乙拉西坦能够调整癫痫幼鼠海马组织5-HT含量及其受体5-HTR1A、5-HTR2C、5-HTR3A表达水平,可能是其保护癫痫幼鼠学习、记忆能力的重要机制之一.“,”Objective To explore the effect of levetiracetam on learning and memory capability of immature rats with epilepsy.Methods Ninety-six immature male clean Wistar rats were selected and randomly divided into four groups.The rats in control group were fed normally,while the rats in the other three groups were prepared for construction of epilepsy model.After successful construction of epilepsy model,the rats in levetiracetam intervention group and carbamazepine intervention group were treated by intragastric administration of levetiracetam suspension and carbamazepine suspension,respectively,the treatment was continued for four weeks.Asp flooding test and water maze test were used to evaluate learning and memory capability.ELISA was used to detect the levels of 5-hydroxytryptamine (5-HT) in hippocampus.Paraformaldehyde heart perfusion experiment and immunofluorescence assay were used to detect the expression levels of 5-HT receptors (5-HTR1A,5-HTR2C,5-HTR3A) in hippocampus.Results After three experiments,stable epilepsy model was obtained,the degree of epilepsy ranged from grade 5 to grade 7.Compared with control group,the numbers of crossing grid and platform and the time of platform stay in the other groups decreased,the time of positioning and navigation prolonged.Compared with model group,the numbers of crossing grid and platform and the time of platform stay in levetiracetam intervention group and carbamazepine intervention group increased,the time of positioning and navigation shortened.Compared with levetiracetam intervention group,the numbers of crossing grid and the time of platform stay in carbamazepine intervention group decreased,the time of positioning and navigation prolonged.There were statistically significant differences among these groups (all P<0.05).Compared with control group,the expression levels of 5-HT,5-HTR1 A,and 5-HTR2C in the other groups decreased,while the expression level of 5-HTR3A increased.Compared with model group,the expression levels of 5-HT,5-HTR1A,and 5-HTR2C in levetiracetam intervention group and carbamazepine intervention group increased,while the expression level of 5-HTR3A decreased.Compared with levetiracetam intervention group,the expression level of 5-HTR1A in carbamazepine intervention group decreased,while the expression level of 5-HTR3A increased.There were statistically significant differences among these groups (all P<0.05).Conclusion Levetiracetam can adjust the expression levels of 5-HT,5-HTR1A,5-HTR2C,and 5-HTR3A in hippocampus,which may be one of the important mechanisms of protective effect on learning and memory capability of immature rats with epileosv.