PERK/eIF2a/CHOP signal pathway involved in the pathogenesis of necrotizing enterocolitis in neonatal rats / 中华实用儿科临床杂志

ABSTRACT

Objective By establishing multivariate necrotizing enterocolitis (NEC) model in newborn rats to study the expression of the related molecules protein kinase R-like ER kinase(PERK),pho-protein kinase R-like ER kinase(p-PERK),eukaryotic translation initiation factor 2 alpha(eIF2a),pho-eukaryotic translation initiation factor 2 alpha (p-eIF2a),CCAAT/enhancer-binding protein-homologous protein (CHOP) in the PERK/eIF2a/ CHOP signaling pathway to explore the pathogenesis of NEC,and in order to provide a theoretical basis for clinical pre-vention and treatment of NEC.Methods One hundred and fifty neonatal Sprague-Dawley (SD) rats were divided into 3 groups according to random number table.NEC groupfed with formula,experienced hypoxia and cold stress,and lipopolysaccharide(LPS) fed via orogastric gavage to induce NEC model.Salubrinal(SAL) groupestabhshing NEC model and intraperitoneal injection of SAL (1 mg/kg).Control groupthe same amount of 9 g/L saline was injected intraperitoneally.Ten rats selected from each group randomly were decapitated at 0,12,24,48 and 72 h,respectively,and intestinal tissues were obtained,intestinal general situation and made pathology scores observed.Expressions of PERK,p-PERK,eIF2a,p-eIF2a,CHOP proteins were detected by Western blot technique and the expression levels of CHOP mRNA gene were detected by real-time polymerase chain reaction.Results The control group had no NEC.The incidence of NEC in NEC group was 90％ (9/10 cases).The incidence of NEC in SAL group was 40％ (4/10 cases).The p-PERK and p-eIF2a protein expressions in NEC and SAL groups were increased with the modeling time.The p-PERK and p-eIF2a protein expressions of NEC and SAL groups were up-regulated compared with the control group (p-PERK1.528 ± 0.264,1.402 ± 0.233 vs.0.303 ± 0.036;p-eIF2a0.969 ± 0.076,1.173 ± 0.066 vs.0.209 ±0.045;P ＜0.05).The p-eIF2a protein expressions of SAL group were higher than those of the NEC group (P ＜ 0.05).The CHOP protein and CHOP mRNA expressions in the NEC and the SAL groups were increased with the modeling time.The CHOP protein and CHOP mRNA expressions of NEC and SAL groups were up-regulated than those of the control group (CHOP protein1.456 ± 0.223,0.929 ± 0.064 vs.0.165 ± 0.026;CHOP mRNA0.343 ±0.035,0.198 ± 0.044 vs.0.017 ± 0.010;P ＜ 0.05).The CHOP protein and CHOP mRNA expressions of SAL group were lower than that in the NEC group (P ＜ O.05).Conclusions The PERK/eIF2a/CHOP signal pathway may participate in NEC,and salubrinal probably by inhibiting p-eIF2a dephosphorylation,and inhibiting CHOP gene and protein expression to work.