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

作　　者：胡灵君 芦起[1,2] HU Lingjun;LU Qi(Department of Neonatology,National Clinical Research Center for Child Health and Disorders,Key Laboratory of Child Development and Disorders of Ministry of Education,Chongqing Key Laboratory of Pediatrics,Children’s Hospital of Chongqing Medical University,Chongqing,400014;Department of Neonatology,Yibin Hospital Affiliated to Children’s Hospital of Chongqing Medical University,Yibin,Sichuan Province,644000,China)

机构地区：[1]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,重庆400014 [2]重庆医科大学附属儿童医院宜宾医院新生儿科,四川宜宾644000

出　　处：《陆军军医大学学报》2024年第12期1387-1394,共8页Journal of Army Medical University

摘　　要：目的探讨自诱导因子-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P4501A1(cytochrome P4501A1,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。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 P4501A1(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-αand 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.

关 键 词：芳香烃受体 自诱导因子-2 坏死性小肠结肠炎 炎症反应 

分 类 号：R-332[医药卫生] R363.22R725.745