发育期大鼠高热惊厥前后海马γ-氨基丁酸B受体亚基表达的变化

目的：研究高热惊厥(febrile seizures，FS)对发育期大鼠脑内γ-氨基丁酸(γ-aminobutyric acid，GABA)B受体亚基GABABR1与GABARR2蛋白表达的影响。方法：采用热水浴诱导大鼠高热惊厥模型。隔日诱导惊厥1次，共诱导10次，末次惊厥后24h处死大鼠。发育期大鼠随机分为3组：对照组(n＝24)，1次高热处理组(n＝28)，10次高热处理组(n＝40)。高热处理组根据是否出现惊厥再分为1次高热惊厥组(FS1，n＝16)与1次高热未惊厥组(F1，n＝12)，10次高热惊厥组(FS10，n＝15)与10次高热未惊厥组(F10，n＝13)。采用免疫组化方法观察不同次数高热惊厥大鼠脑内GABABR1与GABABR2蛋白表达的变化。结果：FS10大鼠海马齿状回、CAl-CA3区GABABRl和GABABR2蛋白表达明显低于F10、F1、FSl和对照组；F10大鼠上述脑区GABABRl和GABABR2蛋白表达低于F1、FS1和对照组；F1及FS1大鼠与对照组相比差异无显著性；海马各区GABABR1与GABABR2表达的改变大部分平行，但10次高热惊厥后GABABR2在CA1—CA3区下降更明显，而GABABR1在齿状回下降更明显。结论：反复高热惊厥及反复高热均可使发育期大鼠脑内GABABR亚基蛋白表达降低，高热惊厥的影响较单纯高热更为明显，提示GABABR亚单位与发育期大鼠高热惊厥及其脑损伤密切相关。GABABR1与GABABR2改变的不平行可能与受体亚单位组合的可塑性改变有关，这种改变可能导致抑制功能的改变。

Effects of recurrent febrile seizures on γ-aminobutyric acid B receptor subunit expressions in the hippocampus of developing rats

OBJECTIVE: To study gamma-aminobutyric acid (GABA) B receptor subunits GABABR1 and GABABR2 protein expression changes after recurrent febrile seizures in the hippocampus of developing rats. METHODS: The rats were randomly divided into hyperthermia-treated group (n = 68) and control group (n = 24). According to the times of treatment, and to whether seizures developed, hyperthermia-treated group were subdivided into 4 groups: F1 (febrile, one-time, n = 12), FS1 (febrile seizure, one-time, n = 16), F10 (febrile, ten-time, n = 13), FS10 (febrile seizure, ten-time, n = 15). Immunohistochemical staining was used to demonstrate GABABR1 and GABABR2 expressions in brain sections (12 microns each). RESULTS: GABABR1 and GABABR2 protein expressions significantly decreased in dentate gyrus and CA1-CA3 neurons in FS10 compared with those in F10, F1, FS1 and control groups. The expressions of GABABR1 and GABABR2 protein showed less intense in F10 than those in FS1, F1 and control groups. No significant differences were observed among F1, FS1 and control group. Throughout the hippocampus, the expressions of GABABR1 and GABABR2 protein largely overlaped. GABABR1 protein expressions decreased seriously as compared with the expressions of GABABR2 protein in dentate gyrus, whereas GABABR2 protein expressions decreased more apparently in hippocampus CA1 and CA3 than that of GABABR1 in FS10. CONCLUSION: Recurrent febrile seizures and recurrent hyperthermia all can make the GABABR receptor protein expression down-regulated in the immature rat brain, and GABABR protein expression decreased more apparently in recurrent febrile seizure groups than that in recurrent hyperthermia groups. These suggest that GABABR subunits may play an important role in the immature rat febrile seizures and the difference between GABABR1 and GABABR2 protein expression changes is possible as a result of subunit reorganization, which may lead to the changes of the inhibitory function.