Significance of endoplasmic reticulum stress-associated gene tribbles pseudokinase 3 in the long-term brain injury in developing epileptic rats
10.3760/cma.j.issn.2095-428X.2019.11.012
- VernacularTitle: 内质网应激分子假性激酶3在发育期癫痫大鼠远期脑损伤中的意义
- Author:
Jing ZHANG
1
;
Ying HAN
1
;
Hongfang JIN
1
;
Yang ZHAO
1
;
Qinrui LI
1
;
Jiong QIN
2
Author Information
1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China
2. Department of Pediatrics, Peking University People′s Hospital, Beijing 100044, China
- Publication Type:Journal Article
- Keywords:
Epilepsy;
Long-term brain injury;
Endoplasmic reticulum stress;
Tribbles pseudokinase 3
- From:
Chinese Journal of Applied Clinical Pediatrics
2019;34(11):854-858
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the significance of endoplasmic reticulum stress-associated gene tri-bbles pseudokinase 3 (TRIB3) in the long-term brain injury in rats with developing epilepy.
Methods:Thirty male SD rats aged 21 days were randomly divided into the control group and the epilepsy group, 15 rats in each group.The rats in the epilepsy group were intraperitoneally injected with kainic acid (10 mg/kg) to induce seizures, while the rats in the control group were injected with the equal volume of 9 g/L saline.The rats in two groups were euthanized at 30 d after kainic acid administration.The damage to the ultrastructure of the cortex were observed by using transmission electron microscopy.Neuronal apoptosis in the cortex of rats was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay.The expression and localization of glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein-homologous protein (CHOP), TRIB3, and the activation of protein kinase B (AKT) in the cortex were examined by using Western blot analysis and immunohistochemistry.
Results:Compared with the control group, the different ultrastructural changes were observed in the cortex in the epilepsy group rats.TUNEL assay indicated that the number of apoptosis cells of cortex in the epilepsy group was increased.The protein levels of GRP78 and TRIB3 were upregulated in the cortex of the epileptic rats (1.280±0.272, 1.725±0.570), compared with the control group (1.000±0.000, 1.000±0.000), and the differences were statistically significant (all P<0.05). There was no significant change in CHOP protein between the control group and the epilepsy group.The level of phosphorylated AKT(p-AKT) was decreased in the cortex of the epilepsy group (0.150±0.047), compared with the control group (1.000±0.000), and the difference was statistically significant (P<0.05).
Conclusions:The brain injury caused by epilepsy in the developing rats can sustain to the stage of mature rats, and the endoplasmic reti-culum stress-associated gene TRIB3 is involved in the pathogenesis of long-term brain damage in the rats with deve-loping epilepsy.