γ-氨基丁酸B受体在反复热性惊厥脑损伤中的作用

Effect of Gamma Aminobutyric Acid B Receptor on Brain Damage Induced by Recurrent Febrile Seizures

目的探讨γ-氨基丁酸B受体(γ-aminobutyricacidBreceptor,GABABR)对反复热性惊厥(febrileseizures,FS)脑损伤的影响。方法SD大鼠随机分为对照组、FS组、FS+氯苯氨丁酸(baclofen)组、FS+法克罗芬(phaclofen)组。采用热水浴诱导大鼠FS,隔日诱导1次,共10次。记录大鼠惊厥潜伏期、持续时间及强度;用原位杂交和免疫组织化学方法分别观察c—fos基因和Fos蛋白表达情况。结果与FS组相比,FS+baclofen组大鼠惊厥潜伏期延长、惊厥持续时间缩短、惊厥强度减轻;而FS+phaclofen组大鼠惊厥潜伏期缩短、惊厥持续时间延长、惊厥强度加重。baclofen于预使c-fos基因和Fos蛋白表达降低,而phaclofen干预使其表达增强。结论应用GABABR激动剂baclofen和抑制剂phaclofen干预研究表明,GABABR与热性惊厥脑损伤的发生、发展密切相关。

Objective To explore the effect of γ-aminobutyric acid B receptor（GABABR）on brain damage induced by recurrent febrile seizures （FS）. Methods Rats were randomly divided into four groups： control group （ 37.0 ℃ water, n = 8）, FS group （45.2℃ water, n = 8）, FS ＋ baclofen group （45.2 ℃ water, n = 8）, FS ＋ phaclofen group （45.2 ℃ water, n = 8）. FS in rats were induced for ten times in a bath of warm water, once every 2 days. The intensity, latency and duration of the seizure in rats were recorded. The expression of c -fos gene and Fos protein were examined by in situ hybridization and irnmunohistochemistry, respectively. Results Compared with those of FS group, the seizure latency gradually prolonged, and the seizure duration was shortened in FS ＋ baclofen group. In FS ＋ pbaclofen group, the seizure latency was shorter and the seizure duration was longer than those of FS group. The seizure intensity was lessened in FS ＋ baclofen group while aggravated in FS ＋ pbaclofen group compared with that of FS group. The expression of c - fos gene and Fos protein increased significantly after recurrent FS. Baclofen down regulated the expression of c - fos gene and Fos protein, while phaclofen enhanced the expression of them. Conclusion The study by using the agonist and the inhibitor of GABABR showed that GABABR might play a crucial role in the development of FS- induced brain damage.