发育期大鼠高热惊厥后γ氨基丁酸B受体亚基表达及结合改变的远期观察  

Long-term alteration ofγ-aminobutyric acid B receptor subunits in immature rats after recurrent febrile seizures

作　　者：韩颖[1] 秦炯[1] 卜定方[2] 常杏芝[1] 杨志仙[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]北京大学第一医院中心实验室,100034

出　　处：《中华儿科杂志》2006年第7期527-530,共4页Chinese Journal of Pediatrics

基　　金：卫生部临床学科重点项目基金(20010912)

摘　　要：目的探讨高热惊厥(febrile seizures,FS)对发育期大鼠脑内γ氨基丁酸B受体(γ- aminobutyric acid B receptor,GABABR)亚基GABABR1与GABABR2表达及结合改变的远期影响。方法采用热水浴诱导大鼠反复惊厥。隔日诱导惊厥1次,共诱导10次。发育期大鼠随机分为正常对照组(n=64)和高热处理组(n=268)。正常对照组大鼠置于37℃水中,高热处理组大鼠置于44．8℃热水中。高热处理组大鼠按其是否出现惊厥又分为高热对照组(H,n=64)和高热惊厥组。隔日诱导惊厥1次,共10次。惊厥组大鼠取惊厥1次(FS1,n=64)和10次(FS10,n=64)者作为实验对象。采用免疫双标记检测GABABR1与GABABR2共位点表达的改变;采用竞争RT—PCR检测GABABR1与GABABR2定量表达的改变;采用免疫共沉淀／Western Blot检测GABABR1与GABABR2结合的改变。结果(1)10次高热处理后,大鼠海马GABABR1和GABABR2的表达明显降低。(2)H组和FS1组大鼠GABABR1和GABABR2表达量及二者结合量在末次处理后7-15 d恢复正常,而FS10组未恢复正常。(3)FS10组在末次处理后30 d GABABR1表达恢复正常,而GABABR2及二者结合量未恢复正常。结论发育期大鼠反复高热惊厥可导致GABABR亚单位GABABR1与GABABR2表达及二者结合量的远期改变。Objective Febrile seizure （FS） is closely related to an altered transmission of γ- aminobutyric acid（GABA）. GABA exerts its effects through ionotropic receptors （GABAAR and GABACR） and metabotropic receptors （GABABR）. GABABRs are located at pre- and postsynaptic sites. Stimulation of postsynaptic receptors generates long-lasting inhibitory postsynaptic potentials （liSPs） that are important for the fine-tuning of inhibitory neurotransmission and caused by an increase in K^＋ conductance. At presynaptic sites, GABABRs mediate a suppression on the release of neurotransmitters such as of GABA or glutamate by inhibiting voltage-sensitive Ca^2＋ channels. The present study aimed to explore the long-term changes of GABAB receptor subunits in immature rats after recurrent febrile seizures. Methods Rats were randomly divided into control group and hypethermia treatment group. The control rats （n = 64） were put into 37℃ water for 5 minutes. Rats with hyperthermia treatment were put into 44. 8℃ water for 5 minutes. If a rat in hyperthermia treatment group showed seizure within 5 min, the rat was taken out of the water as soon as the seizure occurred. Water-immersion was carried out 10 times, once every 2 days. Rats showing 10 seizures （ FS10, n =64） were studied. Rats exposed to hyperthermia for 10 times without seizure were also studied as hyperthermia-only （ H, n = 64） group. Rats showing one seizure at the last time of 10 times of hyperthermia treatment were studied as one-seizure group （FS1 , n =64）. The other rats were studied for other research. The changes of GABABR1 and GABABR2 co-localization were detected by double fluorescence; the quantitative alteration of GABABR1 and GABABR2 were detected by quantitative RT-PCR; the binding of GABABR2 to GABABR1 was detected by immunoprecipitation/Western blot. Results GABABR1, GABABR2, and the binding of GABABR2 to GABABR1 decreased after the last febrile seizure in FS10 group, the expression of GABABR1 returned to normal in later ph

关 键 词：惊厥 发热性 受体 GABA-B 海马 大鼠 

分 类 号：R720.597[医药卫生—急诊医学] R338[医药卫生—儿科]