The role of phosphorylated protein kinase R-like ER kinase in brain tissue of hypoxic-ischemic neonatal rats and the following effect on neuronic apoptosis

Abstract

Objective To investigate the effect and mechanism of phosphorylated protein kinase R-like ER kinase(p-PERK) and C/EBP homologous protein(CHOP) after hypoxic-ischemic brain damage(HIBD). Methods Neonatal 7-day-old Sprague Dawley rats were divided into sham-operation control group and HIBD group(n=30 per group). Each group was divided into 0 h, 6 h and 24 h subgroup after operation(n=10 per group). The ratio of apoptosis of brain cell was measured by flow cytometer and the expression of p-PERK and CHOP were detected by Western blot. Results (1)Apoptosis cell appeared at 6 h in HIBD group, the ratio of cell apoptosis was(2.17±0.19)%.The apoptosis cell obvious increased at 24 h, the ratio of cell apoptosis was(13.42±0.83)%.There was a significant increase in the ratio of apoptosis after HIBD 6 h and 24 h, as compared with sham-operation control group[(0.57±0.06)%(P<0.01)]. (2) The expression of both p-PERK and CHOP was very low in sham-operation control group.In the HIBD group, the expression of both p-PERK and CHOP began to increase at 6 h and increased furthermore at HIBD 24 h. The differences in the expression levels of p-PERK and CHOP in HIBD group among different time points were significant(P<0.01). (3) The expression of p-PERK positively correlated with the expression of CHOP(r=0.997, P< 0.05). Conclusion With the emerging of apoptosis after HIBD, the expression of both p-PERK and CHOP increases.The imbalance in the expression of PERK induces the apoptosis of brain cells in the HIBD of neonatal rats by regulation of CHOP expression. Key words: Hypoxic-ischemic brain damage; Neonatal rats; Protein kinase R-like ER kinase; C/EBP homologous protein; Apoptosis