Inhibition Of P38MAPK Signaling Regulates The Expression Of EAAT2 In The Brain Of Epilepsy Rats

Objective: Observe the expression of EAAT2 in brain tissue of lithium chloride pilocarpine induced epilepsy rats.To clarify the effect of p38 MAPK inhibitor SB203580 on the expression of EAAT2.Methods: Adult male SD rats were divided into the following four groups randomly: normal control group(n = 5),epilepsy group(0h,24 h,3d,1W,2W five time points,n = 5 × 4),SB203580 Group(n = 5)and solvent comparision group(n = 5).The model of epilepsy was established by intraperitoneal injected lithium chloride and pilocarpine through the intraperitoneal.Use the Racine score to evaluate the size of duration and the lasting time and HE staining observe the the histopathological changes.Western Blot,immunohistochemistry and immunofluorescence were used to detect the EAAT2 expression in the each group of brain tissue.Results:1.The consequence of Behavior shows that: After injecting lithium chloride and pilocarpine through the intraperitoneal in 10 minutes solvent control group and SB203580 group were(2.57 ± 0.48,2.55 ± 0.52,0.66 ± 0.48),20 minutes was(3.37±0.50,3.69±0.55,1.75±0.43),and 30 minutes was(4.88±0.46,4.87±0.45,2.87±0.32).The first existing time of the epileptic(62.56 ± 9.22)s in the epileptic seizure group,(58.79 ± 8.41)s in the solvent control group and(28.35 ± 4.00)s in the SB203580 group.The comparison between the epilepsy group and the solvent control group about the scope of Racine and existing time of epileptic has no significance of statistics(P>0.05).And compare with others,SB203580 group shorten the existing time of epileptic exactly and low their scope of Racine exactly,it has the significance of statistics(P<0.01).2.The result of HE staining showed that the structure of hippocampus rats was clear in normal control group,and the size of nucleus was regular and no pathological changes were observed.the nucleus pyknosis and most of the neuronal necrosis emerged in the hippocampus of rats when the time of 3d.3.Western Blot shows :the hippocampus of rats in the normal group and temporal cortex has the EAAT expression.Solvent control group was higher than the normal comparison group after being model in 24 h,when the time is 3d it is on the top.3 days after seizure,the expression of EAAT2 in the SB203580 group was significantly higher than that in the epilepsy group(P <0.05).4.The results of immunohistochemistry showed that the number of EAAT2 positive cells in the normal control group was(12.60 ± 3.44),epilepsy group was(21.00 ± 3.87)SB203580 group was(33.42 ± 9.52).Compared with the normal group,the number of EAAT2 positive cells in the hippocampus rats of the epilepsy group was increased(P <0.05).Compared with the epilepsy group,the number of EAAT2 positive cells in hippocampus rats SB203580 group has increased(P <0.05).Conclusions: p38 MAPK inhibitor SB203580 can increase the expression of EAAT2 in brain tissue of epilepsy rats and reduce the degree of seizure in rats.