Effects Of Progesterone And Extract Of Acori Graminei Rhizoma On γ-am Inobutyric Acid A Receptor α1 Subunit Expression In Cortex Of The Rat After Recurrent Seizures

Objective:To investigate the expression ofγ-am inobutyric acid A receptor(GABAAR)α1 subunit in the cortex of the infantile rats following recurrent seizures and the effects of progesterone and acori graminei rhizoma on them, and discuss the relationship between GABAARα1 subunit and developing brain hurt and the protective mechanisms of progesterone and acori graminei rhizoma on the brain injury.Methods:96 of 7-day-old Sprague-Dawley rats were randomly divided into four groups:the control group, the seizure group, the progesterone intervention group and the acori graminei rhizoma intervention group. Each group had 24 rats that were randomly divided into three groups. Seizures in rats were induced by inhalant flurothyl daily in six consecutive days. Rats in the progesterone intervention group received 16mg/Kg of progesterone through intramuscular injection for 6 days, while rats in the acori graminei rhizoma intervention group received 50mg/Kg of acori graminei rhizome volatile oil through intraabdominal injection for 6 days. Brain tissue was sampled at different time points (ld,3d,7d) in each group after last seizure. The expression ofγ-am inobutyric acid A receptor al subunit proteins in the cortex were detected by immunohistochemistry and Western blot methods.Results:Compared with the control, the acumulatec optical density (AOD) of GABAARα1 subunit immunoreactivity (IR) in the cerebral cortex in seizure rats increased significantly 1 day after recurrent seizures(P<0.05). On PN-15d and PN-19d, the AOD of GABAARα1 subunit in the cerebral cortex in seizure rats increased significantly compared with the control(P<0.01). The AOD of GABAARα1 subunit IR in the cortex in the progesterone intervention rats decreased significantly 3 and 7 days after recurrent seizures compared with the seizure rats (P<0.05). There were no significant differences in the AOD of GABAARα1 subunit IR in the cortex between the progesterone intervention group and the seizure group on ARS-1d (PN-13d)(P>0.05). Comparing with the seizure rats, the AOD of GABAARα1 subunit IR in the cortex in the acori graminei rhizoma intervention group decreased significantly on PN-19d (P<0.05). But on PN-13d and PN-15d there were no significantly differences between the acori graminei rhizoma intervention rats and the seizure rats(P>0.05). Western blot method was used in comparing the protein expression of GABAARα1 subunit in the cortex among the three groups. The expression of GABAARα1 subunit protein increased significantly in the seizure rats compared with that in control on ARS-1d (PN-13d), ARS-3d (PN-15d) and ARS-7d (PN-19d) (P<0.01). The expression of GABAARα1 subunit in the cortex in the progesterone intervention group was significantly lower than that in the seizure group on ARS-3d (PN-15d) and ARS-7d (PN-19) (P<0.01). But the expression of GABAARα1 subunit protein was no significant difference on ARS-1d (PN-13d) (P>0.05). On ARS-7d (PN-19d), the expression of GABAARα1 subunit protein in the acori graminei rhizoma intervention group was significantly decreased than that in the seizure group (P<0.01), but the expression was no significant difference on ARS-1d (PN-13d) and ARS-3d (PN-15d) (P>0.05).Conclusions:①Recurrent seizures in neonatal rats modify GABAARα1 subunit expression in the cortex of rats. This phenomenon raised the possibility that increased GABAARα1 subunit expression might play an important role in developmental brain injury.②The decrease of the abnonnal levels of GABAARα1 subunit in the cortex is probably related to the protective effects of progesterone and acori graminei rhizoma on the infantile brain injury induced by seizures.