组胺H3受体拮抗剂对大鼠难治性癫痫的治疗作用  

Anti-convulsion action of histamine H3 receptor antagonists to rat model with intractable epilepsy

作　　者：宋晓颖[1,2] 王江涛[1] 梁东[1] 

机构地区：[1]吉林大学第一医院儿内二科,吉林长春130021 [2]辽宁省大连市中心医院儿科,辽宁大连116033

出　　处：《吉林大学学报（医学版）》2009年第3期494-498,F0003,共6页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅科研基金资助课题(200505213)

摘　　要：目的：探讨中枢组胺（HA）的抗惊厥作用和组胺H3受体（H3R）拮抗剂对难治性癫痫的治疗作用。方法：88只生后12d Wistar大鼠随机分成3组：空白对照组、N-甲基-D天门冬氨酸（NMDA）模型组和盐酸培他啶（BH）组（又分为小剂量BH组和大剂量BH组）。NMDA组和BH组腹腔注射NMDA，建立婴幼儿难治性癫痫动物模型，BH组同时给予150和300mg·kg^-1BH。用药后每天观察痫性发作和行为改变；分别应用荧光法和免疫组化法检测第2和4周末大鼠脑皮质、海马HA含量和H3R分布情况。结果：NMDA模型组和BH组12～17日龄Wistar鼠引出甩尾等自动症及前弓反张发作，18～25日龄的Wistar鼠只有自动症；BH组较NMDA模型组甩尾等自动症和前弓反张发作的发生率降低（P〈0．05）、潜伏期延长（P〈0．05），且大剂量BH组较小剂量BH组潜伏期延长更明显（P〈0．05）。实验第2周末，与空白对照组比较，NMDA模型组皮质及海马HA含量降低（P〈0．05），HaR阳性细胞表达率升高（P〈0．05）；与NMDA模型组比较，BH组皮质及海马区HA含量升高（P〈0．05），H3R阳性细胞表达率降低（P〈0．05），且大剂量BH组较小剂量BH组变化更明显（P〈0．05）；实验第4周末，各组间不同脑区HA含量的变化程度有所减低，但NMDA模型组与BH组比较差异仍有显著性（P〈0．05）；各组间不同脑区H3R阳性细胞表达率比较差异无显著性（P〉0．05）。结论：NMDA诱发的Wistar大鼠惊厥发作与人类婴儿痉挛临床表现相似，符合难治性癫痫动物模型标准；脑内HA含量越低则癫痫发生率越高，组胺H3R拮抗剂对大鼠难治性癫痫有一定的治疗作用。Objective To explore the anti-convulsion action of histamine （HA） in the central system and treatment of histamine Ha receptor （H3R） antagonists to rat model with intractable epilepsy. Methods 88 Wistar rats （12- day-old） were randomly divided into three groups： normal control group, N-methyl-D-aspartate （NMDA） group and betahistine （BH） groups （including high and low dose BH groups）. Wistar rats received an intraperitoneal NMDA administration to make animal model of intractable epilepsy at infant period and toddler age. After that, the rats were observed daily for latencies and incidences to two NMDA-dependent stereotypical behaviors. The HA content of each brain region was determined with fluorimetry, and H3R were evaluated with immunohistochemical method. Results The automatisms including tail twisting and emprosthotonus seizures of （12- 17） -day-old rats were observed in NMDA and BH groups. The rats, aged 18-25 d, became quiet following automatisms rather than emprothotonic. Compared with NMDA group, BH groups had longer latencies and lower incidences of tail twisting and emprosthotonus （P〈0.05）. At the end of the 2nd week, compared with normal control group, the HA contents of cortex and hippocampus in NMDA group were lower （P〈0.05）, and the expression rates of H3 R positive cells were higher （P〈0. 05）. Compared with NMDA group, the HA contents of cortex and hippocampus in BH groups were higher （P〈0.05）, the expression rates of H3R positive cells were decreased （P〈0.05）. At the end of the 4th week, the changes of HA contents between every two groups became less. There were significant differences of the HA contents between NMDA group and BH groups （P〈0.05）. But there were no significant differences of the expression rates of H3R positive cells between every two groups （P〉 0.05）. Conclusion The NMDA-indueed model is similar to the clinical manifest of human West syndrome. It is up to animal model of intractable epilepsy at infant period a

关 键 词：组胺 组胺H3 受体拮抗剂 难治性癫痫 模型 动物 

分 类 号：R-332[医药卫生] R742.1