The relationships of the levels of receptor-interacting protein kinase 3 and mixed lineage kinase domain-like protein in peripheral blood with the severity of necrotizing enterocolitis in newborns
Objective To analyze the expressions of receptor-interacting protein kinase 3(RIPK3)and mixed lineage kinase domain-like protein(MLKL)in peripheral blood of neonates with necrotizing enterocolitis(NEC)and their relationships with the severity of the disease.Methods Nine-ty-two children with NEC were selected and divided into NEC group,and further divided into mild group(grade Ⅰ,n=60)and severe group(grade Ⅱ to Ⅲ,n=32)according to the severity of the disease.Another 60 children with inguinal hernia were selected as control group.Real-time fluores-cence quantitative polymerase chain reaction was used to detect the expressions of RIPK3 mRNA and MLKL mRNA in peripheral blood.Pearson correlation analysis was used to determine the correlation between RIPK3 mRNA and MLKL mRNA expression in peripheral blood of the NEC group.Western blot was used to detect the expression of RIPK3 and MLKL proteins in ileal tissues of NEC and nor-mal ileal tissues.Multivariate Logistic regression analysis was used to identify independent risk fac-tors for severe NEC.The receiver operating characteristic curve was plotted to analyze the value of peripheral blood RIPK3 mRNA and MLKL mRNA alone and their combination for predicting severe NEC.Results The relative expression levels of RIPK3 mRNA and MLKL mRNA in peripheral blood of the NEC group were significantly higher than those in the control group[(2.41±0.52)versus(1.02±0.21),(3.03±0.64)versus(0.93±0.20),P<0.001].The relative gray val-ues of RIPK3 and MLKL proteins in ileal tissues of NEC were significantly higher than those in nor-mal ileal tissues[(1.20±0.21)versus(0.34±0.12),(1.13±0.24)versus(0.32±0.11),P<0.05].There was a positive correlation between the relative expression level of RIPK3 mRNA and MLKL mRNA in peripheral blood of children with NEC(r=0.623,P<0.001).The propor-tion of children with severe NEC complicated by pneumoperitoneum,multiple organ dysfunction syn-drome,and sepsis,as well as the relative expression levels of RIPK3 mRNA and MLKL mRNA were significantly higher in the severe NEC group than in the mild NEC group(P<0.05).The relative expression levels of RIPK3 mRNA and MLKL mRNA were independent risk factors for severe NEC(P<0.05).The area under the curve for combined prediction of severe NEC by RIPK3 mRNA and MLKL mRNA in peripheral blood was larger than that for individual prediction(Z=4.127,4.261,P<0.05).Conclusion The expression levels of RIPK3 mRNA and MLKL mRNA in peripheral blood are elevated in neonates with NEC,and both are associated with the severity of NEC.The combined detection of RIPK3 mRNA and MLKL mRNA has a higher predictive value for severe NEC.
necrotizing enterocolitisreceptor-interacting protein kinase 3mixed lineage ki-nase domain-like proteinmultiple organ dysfunction syndromesepsis