托吡酯、丙戊酸钠、苯巴比妥预防动物反复热性惊厥脑损伤的作用  

Preventive effects of topiramate,phenobarbital and valproate sodium on repetitive febrile convulsion-induced brain damage in animals

作　　者：李娟[1] 黄志[1] 陈琼[1] 张小萍[1] 

机构地区：[1]重庆医科大学儿童医院,重庆400014

出　　处：《第四军医大学学报》2008年第22期2045-2048,共4页Journal of the Fourth Military Medical University

摘　　要：目的:探讨托吡酯(TPM),丙戊酸钠(VPA),苯巴比妥(PB)对大鼠反复热性惊厥(CFC)脑损伤的保护作用,并比较它们之间的差异.方法:清洁级SD大鼠,采用热水浴升高大鼠体温的方法,制备CFC大鼠模型.实验分为TPM组、PB组、VPA组、生理盐水(NS)组和正常对照组.在对TPM组,PB组,VPA组,NS组实行药物干预的同时,每2d使大鼠热性惊厥(FC)1次,观察大鼠对FC的反应情况,并对CFC后大鼠脑海马组织进行电镜观察和血清神经元特异性烯醇化酶(NSE)水平检测,以了解脑损伤的发生情况;采用水迷宫方法观察大鼠学习记忆的改变情况.结果:大鼠血清NSE浓度TPM组,PB组,VPA组,正常对照组分别为(2.0±0.26),(2.5±0.35),(2.3±0.24),(1.52±0.24)mg/L,以NS组(3.30±0.31)mg/L的浓度最高,与其他各组比较,差异具有统计学意义(P<0.05).水迷宫实验结果以NS组潜伏期(53.0±35.0)s最长,正常对照组潜伏期(12.1±12.6)s最短,与PB组VPA组比较,差异具有统计学意义(P<0.05);TPM组(22.8±29.0)s与正常对照组间差异无统计学意义(P>0.05).脑组织超微结构表现NS组海马CA1区及门区神经元细胞核为中-重度肿胀,神经元出现坏死现象,同时伴有线粒体肿胀,嵴模糊不清,甚至消失.而TPM组,PB组,VPA组表现为海马CA1区及门区神经元基质多均匀,细胞核为轻-中度肿胀,少量线粒体出现嵴模糊不清,肿胀.结论:TPM,VPA,PB对CFC造成的大鼠脑损伤均具有保护作用,可以改善FC性脑损伤的程度,以TPM预防和减轻CFC所导致的惊厥性脑损伤的效果最好.AIM： To explore whether topiramate （TPM）, phenobarbital（PB） and valproate sodium（VPA） have protection or improvement on febrile convulsion-induced brain damage in animals, and compare the variances in them. METHODS： Sprague-Dawley rats were randomly divided into TPM, PB, VPA, NS and normal groups. Febrile convulsions were induced with hyperthermal bath at 45℃ every other day at the same time of oral administration. Manifestation of convulsions and differences were observed in all these groups. After nine convulsions were induced, the ultrastruetural changes of the hippocampal neurons were observed under the electron microscope, and the level of neuron-special enolase（NSE） in blood serum was detected, By a water maze test, latencies to escape onto the platform were recorded to observe the learning ability. RESULTS： The level of NSE in blood serum was significantly heightened more in rats in TPM [ （ 2.0 ± 0.26 ） mg/L, P〈0.053, PB [（2.5 ±0.35） mg/L, P 〈0.013 and VPA [ （2.3±0.24） mg/L, P 〈0.01 ] groups than in the normal group [ （ 1.52 ± 0.24 ） mg/L], but was significantly lower than in NS group[ （3.30 ±0.31 ） mg/L,P 〈 0.01 ]. In water-maze lab, significant difference in lateneies to escape onto the platform was observed between NS group [ （53.0±35.0） s] and other groups （ P 〈0.05 or 0.01 ） , and the same was observed between VPA or PBgroup and normal group [ （12. 1±12.6） s, P〈0.05 or 0.01 ]. No significant difference was observed between TPM group [ （22.8 ± 29.0 ） s ] and the normal group （ P 〉 0. 05 ）. In the hippocampal CA1 and hile neurons of NS group rats, some mitochondria swelled, the ridge obscured or disappeared, and nucleus swelled moderately to heavily. Necrosis was also observed in neurons. In the hippocampal CA1 and hile neurons of drug-intervention rats, the matrix distributed well, nucleus swelled mildly to moderately, little mitochondria swelled or the ridge was obscured. CONCLUSION ： Continuous administration of 3

关 键 词：托吡酯 惊厥 发热性 脑损伤 

分 类 号：R720.597[医药卫生—急诊医学]