【摘要】 目的观察海人酸(KA)诱导的实验性癫癎(EP)大鼠发作后海马γ-氨基丁酸B受体(GABABR)亚单位mRNA表达及其激动剂巴氯芬的影响。方法运用原位杂交法检测各实验组大鼠EP发作后及巴氯芬干预后海马区GABABR亚单位GAR1a及GAR2 mRNA表达。结果KA致癎早期(6~12h)2种亚单位mRNA表达水平广泛下降,至1d仍明显低于对照组(均P<0.05),但齿状回(DG)区mRNA表达开始回升,3d后表达水平已明显高于对照组(P<0.05),而CA1与CA3区表达仍维持低水平(均P<0.05),但其表达水平渐向对照组水平恢复。巴氯芬干预后亚单位表达明显下降的时间点延迟,且表达水平明显高于非干预的致癎组(P<0.05~0.01)。结论致癎鼠2种亚单位表达下降后又上调为颞叶EP的内源性自我保护机制;巴氯芬促进2种亚单位表达,增强GABA抑制作用,有利于控制EP,为筛选针对GABABR亚单位的抗癎药提供新途径。更多还原

【Abstract】 Objective To explore the expression of Gamma-aminobutyric acid B recepter (GABABR) subunits mRNA and the effects of its agonist Baclofen in hippocampus after KA induced seizures,of experimental epileptic rats.Methods The GABABR subunits GAR1a及GAR2 mRNAs expression were determined in hippocampus of each experimental group after epileptic seizure and Baclofen interference by hybridization in situ. Results In early(6~12 h) time of KA induced epileptic rats, the mRNA levels of both receptor subunits in hippocampal formation were found downregulation widespreadly (all P<0.05).One day after onset the decrease of mRNA levels persisted in sectors CA1 and CA3,however, mRNA levels in the dentate gyrus increased rapidly and then higher than the levels of control group(P<0.05),and mRNA levels in sector CA3 partially recovered to control levels at late time points.The time point of decreases of subunit mRNA expression in baclofen interference group was later than that of KA induced seizure group.The mRNA expression levels in baclofen intereference group were singnificantly higher than that of KA induced seizure group(P<0.05~0.01). Conclusions This is the result of endogenous antiepileptic mechanism of TLE for the early downregulation of GABABR mRNAs and then upregulation of GABABR subunits mRNAs.Baclofen can elevate expression levels of both subunits,and enhance GABA mediated inhibition which may promote binding of GABA to the GABA receptor, and benefit for controlling the development of EP.The findings of subunit changes may provid the way for screening the new antiepileptic drug of a single receptor subunit.更多还原