托吡酯联合奥卡西平对癫痫患儿的疗效及机制研究  

Study on the efficacy and mechanism of topiramate combined with oxcarbazepine in children with epilepsy

作　　者：李学渊 郝凌坤 冯旭 李雯 岳淑敏 田龙 LI Xueyuan;HAO Lingkun;FENG Xu(Department of Neurology,Zhangjiakou First Hospital,Zhangjiakou 075000,China)

机构地区：[1]张家口市第一医院神经内科,075000 [2]张家口市第一医院检验科,075000 [3]张家口市第一医院儿科,075000

出　　处：《临床神经病学杂志》2025年第1期42-47,共6页Journal of Clinical Neurology

基　　金：张家口市重点研发计划项目(2322173D)。

摘　　要：目的探讨托吡酯联合奥卡西平对癫痫患儿的疗效及机制。方法通过pharm GKB数据库分析托吡酯和奥卡西平的靶向基因;通过GeneCards数据库筛选患儿癫痫的靶基因;采用Cytoscape 3.9.1软件构建药物-疾病-靶基因网络图。选取首次就诊的癫痫患儿83例,根据使用药物的不同分为托吡酯组和联合用药组。采用ELISA法观察两组患者血清哺乳动物雷帕霉素靶蛋白(mTOR)、表皮生长因子受体(EGFR)、氮酶调节因子3样蛋白(NPRL3)的水平,记录患儿的EEG及疗效。结果托吡酯联合奥卡西平治疗患儿癫痫的靶向基因有mTOR、EGFR和NPRL3。联合用药组与托吡酯组癫痫发作率差异无统计学意义(χ^(2)=3.239,P=0.072)。联合用药组疗效显著优于托吡酯组(χ^(2)=5.817,P=0.049)。联合用药组的尖波波率(SWR)≤2的比率显著高于托吡酯组(P=0.018)。联合用药组及托吡酯组的尖波定位差异有统计学意义(P=0.002),尖波发生区域差异无统计学意义(P>0.05)。与托吡酯组比较,联合用药组治疗1个月、3个月、6个月的尖波数量显著减少,治疗1个月、3个月、5个月、6个月的尖波清除速率显著升高(P<0.05~0.01)。联合用药组及托吡酯组治疗前mTOR、EGFR和NPRL3水平差异无统计学意义(均P>0.05)。与托吡酯组比较,联合用药组治疗后mTOR、EGFR水平显著降低(P=0.028,P=0.006),NPRL3水平显著升高(P=0.007)。生存分析结果显示,中位癫痫持续时间为6(5,6)个月,癫痫发作率为55.42%。与mTOR≤9.93(16.7%)相比,mTOR>9.93(93.1%)发生癫痫的比率显著升高(χ^(2)=11.430,P<0.001)。结论托吡酯联合奥卡西平可减少尖波峰值和波率,进而改善癫痫发作,机制可能与mTOR、NPRL3、EGF的水平有关。Objective To investigate the efficacy and mechanism of topiramate combined with oxcarbazepine in children with epilepsy.Methods The targeted genes of topiramate and oxcarbazepine were analyzed by pharm GKB database;targeted genes of epilepsy in children were screened by GeneCards database;the drug-disease-target gene network map was constructed using Cytoscape 3.9.1 software.A total of 83 children with epilepsy were enrolled and treated for the first time,which were divided into topiramate group and combined drugs group according to the different drugs used.The level of serum mechanistic target of rapamycin(mTOR),epidermal growth factor receptor(EGFR),nitrogen permease regulator 3-like protein(NPRL3)of two groups were observed by ELISA,and the EEG and therapeutic effect were recorded.Results mTOR,EGFR,NPRL3 were the target genes of topiramate combined with oxcarbazepine in the treatment of epilepsy in children.There was no significant difference in seizure rate between the combined drugs group and topiramate group(χ^(2)=3.239,P=0.072).The efficacy of combined drug group was significantly better than that of the topiramate group(χ^(2)=5.817,P=0.049).The rate of standing wave ratio(SWR)≤2 in EEG spike in the combined drug group was significantly higher than that in the topiramate group(P=0.018).There was different in spike location between combined drug group and topiramate group(P=0.002),while not different statistically in spike region of two groups(P>0.05).Compared with those in topiramate group,the number of sharp waves in the combination group was significantly reduced at 1 month,3 months and 6 months after treatment,and the sharp wave clearance rate was significantly increased at 1 month,3 months,5 months and 6 months after treatment(P<0.05-0.01).There was no significant difference in levels of mTOR,EGFR,NPRL3 between the combination group and topiramate groups before treatment(all P>0.05).Compared with those in topiramate group,the levels of mTOR,EGFR in combined drug group after treatment were significa

关 键 词：癫痫 尖波清除速率 哺乳动物雷帕霉素靶蛋白 氮酶调节因子3样蛋白 

分 类 号：R742.1[医药卫生—神经病学与精神病学]