反复热性惊厥过程中γ-氨基丁酸B受体对硫化氢的调节作用

Gamma-aminobutyric acid B receptor regulates the expression of hydrogen sulfide / cystathionine-β-synthase system in recurrent febrile seizures

摘要:

目的：热性惊厥(febrile se izure,FS)是婴幼儿时期最常见的惊厥性疾患之一,阐明其发生机制一直是该领域的重要研究课题。该课题前期的研究证明,γ-氨基丁酸B受体(-γam inobutyric ac id B receptor,GABABR)亚基和气体信号分子硫化氢(H2S)均在反复热性惊厥中发挥了重要作用。该文使用GABABR激动剂ba-c lofen,抑制剂Phac lofen,探讨GABABR对FS大鼠硫化氢/胱硫醚-β-合成酶(cystath ion ine--βsynthase,CBS)体系表达的影响。方法：大鼠随机分为对照组,FS组,FS+bac lofen组,FS+phac lofen组。采用热水浴诱导大鼠FS,隔日诱导1次,共10次。采用分光光度计法测定大鼠血浆中H2S含量;用原位杂交方法观察CBS mRNA表达情况;用免疫组化方法观察CBS蛋白表达情况。结果：FS+bac lofen组H2S含量较FS组升高427.45±15.91μmol/L vs362.14±19.71μmol/L,同时CBS表达也较FS组增强;而FS+phac lofen组H2S含量较FS组降低189.72±21.53μmol/L vs 362.14±19.71μmol/L,同时CBS表达也较FS组减弱。结论：反复热性惊厥过程中,GABABR的改变可影响H2S/CBS体系的表达。

Abstract:

OBJECTIVE: Febrile seizure(FS) is one of the most common seizure types in children.Our previous studies have demonstrated that both γ-aminobutyric acid B receptor (GABA_BR) and hydrogen sulfide (H_2S) are involved in the pathogenesis of FS.This study was designed to explore the effect of GABA_BR on H_2S / cystathionine-β-synthase (CBS) system in recurrent FS. METHODS: Sixty-four Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control (37℃ water bath exposure), FS, FS+baclofen (GABA_BR excitomotor), and FS+phaclofen (GABA_BR inhibitor) groups (n=16 each). FS was induced by warm water bath exposure (45.2℃), once every 2 days, 10 times in total. The plasma level of H_2S was detected by the spectrophotometer. The expression of CBS mRNA was examined by in situ hybridization. The expressions of CBS protein was observed by immunohistochemistry. RESULTS: The plasma level of H_2S increased in the FS + baclofen group (427.45±15.91 μmol/L) but decreased in the FS+phaclofen group (189.72±21.53 μmol/L) compared with that in the FS group (362.14±19.71 μmol/L). The expressions of CBS mRNA and protein were up-regulated in the FS+baclofen group but were down-regulated in the FS+phaclofen group compared with those in the FS group. CONCLUSIONS: GABA_BR modulated the expression of H_2S/ CBS system in recurrent FS.