Protective effects of interleukin-1 receptor associated kinase 1/4 inhibitor on intestinal tissues of neonatal rats with necrotizing enterocolitis / 中华实用儿科临床杂志

ABSTRACT

Objective To establish an appropriate neonatal rat model with necrotizing enterocolitis (NEC) and to investigate the protective effects of interleukin-1 receptor associated kinase (IRAK) 1/4 inhibitor on intestinal tissue of neonatal rats with NEC.Methods Thirty-six newborn SD rats were randomly divided into normal control group,NEC model group and IRAK1/4 inhibitor group,12 rats in each group.The rats in normal control group were raised by their mother and they did not receive any intervention.The rats of NEC model group were given artificial feeding,under hypoxia and cold stress.The IRAK1/4 inhibitor group were given IRAK1/4 inhibitor intervention,and also given artificial feeding,under hypoxia and cold stress.Three days later,all rats were sacrificed and intestinal tissues were obtained.The histopathological changes in ileocecal tissues were evaluated by pathological score after hematoxylin-eosin staining.The levels of interleukin (IL)-1β,IL-6 and tumor necrosis factor (TNF)-α in intestinal tissues were detected by enzyme-linked immunosorbent assay.Results The rats of NEC model group presented abdominal distention,diarrhea (partly with mucous bloody stool),decreased activity,poor response,lethargy and other symptoms,and the extent was gradually worsened;the rats in IRAK1/4 inhibitor group also had abdominal distention,diarrhea,decreased activity,poor response and other symptoms,but the symptoms emerged later and milder.The histopathological score of intestinal tissues of normal control group was (0.33 ± 0.49) scores,NEC model group was (3.08 ± 0.99) scores,and IRAK1/4 inhibitor group was (1.75 ±0.96) scores.The histopathological scores of NEC model group and IRAK1/4 inhibitors group were significantly higher than those in normal control group (all P ＜ 0.01),and the histopathological scores of IRAK1/4 inhibitor group were significantly lower than those in the NEC model group (P ＜ 0.01).The levels of IL-1β,IL-6 and TNF-α in normal control group separately were (128.76 ± 27.25) ng/L,(0.41 ± 0.10) ng/L,(6.93 ± 1.79) ng/L,respectively;the levels of NEC model group separately were (410.99 ± 44.16) ng/L,(1.79 ± 0.18) ng/L,(44.39 ± 6.00) ng/L;the levels of IRAK1/4 inhibitor group separately were (256.23 ±41.29) ng/L,(1.05 ±0.19) ng/L,(21.45 ± 6.36) ng/L,respectively.The levels of IL-1β,IL-6 and TNF-α of NEC model group had significant differences compared with those of normal control group,respectively (all P ＜0.01);the levels of IL-1β3,IL-6 and TNF-α of IRAK1/4 inhibitor group had significant differences compared with those of normal control group,respectively (all P ＜ 0.01);the levels of IL-1β,IL-6 and TNF-α of IRAK1/4 inhibitor group had significant differences compared with those of NEC model group (all P ＜ 0.01),respectively.Conclusions IRAK1/4 inhibitor has some protective effects on the intestinal tissues of neonatal rats with NEC,which can reduce the damage to the intestinal tissues,and decrease the secretion of inflammatory cytokines like IL-1β,IL-6 and TNF-α.