Activation of aryl hydrocarbon receptor by autoinducer-2 alleviates intestinal injury in a neonatal mouse model of necrotizing enterocolitis
10.16016/j.2097-0927.202309140
- VernacularTitle:自诱导因子-2激活芳香烃受体缓解新生小鼠坏死性小肠结肠炎肠道损伤
- Author:
Lingjun HU
1
;
Qi LU
Author Information
1. 400014 重庆,重庆医科大学附属儿童医院新生儿科,国家儿童健康与疾病临床医学研究中心,儿童发育疾病研究教育部重点实验室,儿科学重庆市重点实验室
- Keywords:
aryl hydrocarbon receptor;
autoinducer-2;
necrotizing enterocolitis;
inflammatory response
- From:
Journal of Army Medical University
2024;46(12):1387-1394
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of autoinducer-2(AI-2)in relieving intestinal injury in neonatal mouse model of necrotizing enterocolitis(NEC).Methods Thirty-six 7-day-old C57BL/6J mice were randomly divided into Control group(fed by mother mice),NEC group(NEC model induced by formula+lipopolysaccharide administration,hypoxia and cold stress),and NEC+AI-2 group(AI-2 solution added to the modeled formula milk),with 12 mice in each group.The body weight and survival rate of each group were recorded during the modeling period.In 3 d after modeling,the mice were euthanized,and the histopathological changes in the terminal ileum were observed using HE staining.The mRNA expression levels of aryl hydrocarbon receptor(AHR),cytochrome P450 1A1(CYP1A1),TNF-α,IL-6 and IL-22 in intestinal tissue were detected with RT-qPCR.The protein levels of AHR and CYP1A1 in intestinal tissues were measured with Western blotting.The contents of TNF-α,IL-6 and IL-22 in intestinal tissues were detected using enzyme-linked immunosorbent assay(ELISA).Results The survival rate of neonatal rats was significantly higher in the NEC+AI-2 group than the NEC group(91.7％vs 66.7％,P＜0.05).The NEC+AI-2 group had obviously lower intestinal pathological injury score(1.33±0.21 vs 2.67±0.33,P＜0.05),increased mRNA and protein levels of AHR and CYP1A1 in intestinal tissues(P＜0.05),decreased expression levels of pro-inflammatory factors TNF-α and IL-6 in intestinal tissues(P＜0.05),while increased expression level of anti-inflammatory factor IL-22(P＜0.05)when compared with the NEC group.Furthermore,the expression and activation of intestinal AHR were negatively correlated with the intestinal pathological injury score(P＜0.001).Conclusion AI-2 alleviates intestinal injury in neonatal mice with NEC by activating AHR to regulate inflammatory response.
