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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
Activation of aryl hydrocarbon receptor by autoinducer-2 alleviates intestinal injury in a neonatal mouse model of necrotizing enterocolitis
- 陆军军医大学学报 2024年46卷第12期 页码：1387-1394
- 作者机构：
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
2.644000 四川 宜宾，重庆医科大学附属儿童医院宜宾医院新生儿科
- 作者简介：
[芦起，E-mail: qilu_qi@163.comLU Qi, E-mail: qilu_qi@163.com
- 基金信息：
DOI：10.16016/j.2097-0927.202309140
中图分类号： R-332;R363.22;R725.745收稿：2023-09-26，
修回：2023-11-22，
纸质出版：2024-06-30
- 稿件说明：
移动端阅览
胡灵君, 芦起. 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[J]. 陆军军医大学学报, 2024,46(12):1387-1394.
Lingjun HU, Qi LU. Activation of aryl hydrocarbon receptor by autoinducer-2 alleviates intestinal injury in a neonatal mouse model of necrotizing enterocolitis[J]. Journal of Army Medical University, 2024, 46(12): 1387-1394.
胡灵君, 芦起. 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[J]. 陆军军医大学学报, 2024,46(12):1387-1394. DOI： 10.16016/j.2097-0927.202309140.
Lingjun HU, Qi LU. Activation of aryl hydrocarbon receptor by autoinducer-2 alleviates intestinal injury in a neonatal mouse model of necrotizing enterocolitis[J]. Journal of Army Medical University, 2024, 46(12): 1387-1394. DOI： 10.16016/j.2097-0927.202309140.
摘要
目的
2
探讨自诱导因子-2(autoinducer-2
AI-2)缓解新生鼠坏死性小肠结肠炎(necrotizing enter colitis
NEC)模型肠道损伤的作用机制。
方法
2
将36只7 d龄C57BL/6J小鼠随机分为(
n
=12): 对照组(Control组
由母鼠喂养)、NEC组(采用配方奶+脂多糖灌胃、缺氧和冷应激的方法诱导新生鼠NEC模型)及NEC+AI-2组(建模的配方奶中添加AI-2溶液)。记录造模期间各组小鼠体质量及存活率。建模3 d后处死小鼠
HE染色观察末端回肠组织病理学改变; RT-qPCR检测肠组织芳香烃受体(aryl hydrocarbon receptor
AHR)、细胞色素P450 1A1(cytochrome P450 1A1
CYP1A1)、肿瘤坏死因子-α(tumor necrosis factor-α
TNF-α)、白细胞介素-6(interleukin-6
IL-6)、白细胞介素-22(interleukin-22
IL-22)基因的表达水平; Western blot检测肠组织AHR、CYP1A1蛋白表达水平; 酶联免疫吸附试验(ELISA)检测肠组织中TNF-α、IL-6、IL-22蛋白表达水平。
结果
2
与NEC组相比
NEC+AI-2组新生鼠存活率增加(91.7%
vs
66.7%
P
<
0.05);肠道病理损伤评分降低(1.33±0.21
vs
2.67±0.33
P
<
0.05);肠组织中AHR、CYP1A1在基因及蛋白表达水平均明显升高(均
P
<
0.05);肠组织中促炎因子TNF-α、IL-6表达水平降低(均
P
<
0.05)
抑炎因子IL-22表达水平增加(均
P
<
0.05)。肠道AHR表达及活化与肠道病理损伤评分呈明显的负相关关系(
P
<
0.001)。
结论
2
AI-2可通过激活肠道中AHR调节炎症反应缓解NEC新生鼠的肠道损伤。
Abstract
Objective
2
To investigate the mechanism of autoinducer-2(AI-2) in relieving intestinal injury in neonatal mouse model of necrotizing enterocolitis (NEC).
Methods
2
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
2
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
2
AI-2 alleviates intestinal injury in neonatal mice with NEC by activating AHR to regulate inflammatory response.
关键词
Keywords
references
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