芳香烃受体活化对全肠外营养小鼠肠屏障损伤的保护作用研究

刘星宇; 肖卫东; 陈弈辉; 韩奔; 王维; 王建

doi:10.16016/j.2097-0927.202210111

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芳香烃受体活化对全肠外营养小鼠肠屏障损伤的保护作用研究

基础医学 | 更新时间：2026-01-09

- 芳香烃受体活化对全肠外营养小鼠肠屏障损伤的保护作用研究
- Protective effects of aryl hydrocarbon receptor activation on intestinal barrier damage in a mouse model of total parenteral nutrition
- 陆军军医大学学报 2023年45卷第5期页码：400-406
- 作者机构：
  
  1.400037 重庆, 陆军军医大学(第三军医大学)第二附属医院营养科
  2.400037 重庆, 陆军军医大学(第三军医大学)第二附属医院普外科
- 作者简介：
  
  [王建，E-mail: wangjian_1996@aliyun.com WANG Jian, E-mail: wangjian_1996@aliyun.com
- 基金信息：
  
  国家自然科学基金面上项目(82270585);军事医学高新技术培育项目(CX2019JS212)
- DOI：10.16016/j.2097-0927.202210111
  中图分类号： R322.45;R459.3;R914.4
- 收稿：2022-10-14，
  
  修回：2023-01-02，
  
  纸质出版：2023-03-15
- 稿件说明：
移动端阅览
刘星宇, 肖卫东, 陈弈辉, 等. 芳香烃受体活化对全肠外营养小鼠肠屏障损伤的保护作用研究[J]. 陆军军医大学学报, 2023,45(5):400-406.

Xingyu LIU, Weidong XIAO, Yihui CHEN, et al. Protective effects of aryl hydrocarbon receptor activation on intestinal barrier damage in a mouse model of total parenteral nutrition[J]. Journal of Army Medical University, 2023, 45(5): 400-406.
刘星宇, 肖卫东, 陈弈辉, 等. 芳香烃受体活化对全肠外营养小鼠肠屏障损伤的保护作用研究[J]. 陆军军医大学学报, 2023,45(5):400-406. DOI： 10.16016/j.2097-0927.202210111.

Xingyu LIU, Weidong XIAO, Yihui CHEN, et al. Protective effects of aryl hydrocarbon receptor activation on intestinal barrier damage in a mouse model of total parenteral nutrition[J]. Journal of Army Medical University, 2023, 45(5): 400-406. DOI： 10.16016/j.2097-0927.202210111.

摘要

目的

探讨6-甲酰基吲哚并[3

2-B]咔唑(6-ForMylindolo[3

2-b]carbazole，FICZ)活化芳香烃受体(AhR)对全肠外营养(total parenteral nutrition，TPN)小鼠肠屏障损伤的保护作用及相关机制。

方法

将18只小鼠经颈外静脉置管输液后随机分为3组：对照组、TPN组、TPN+FICZ(1 μg/d)组；TPN和TPN+FICZ组禁食输注等量营养液，对照组正常进食并输注等量生理盐水；7 d后比较置管前后小鼠体质量变化，取外周血检测肠屏障标志物，处死小鼠观察完整小肠长度和肠黏膜的形态学改变，取末端回肠组织检测肠屏障相关蛋白和mRNA表达。

结果

与对照组比较，TPN组小鼠体质量下降明显，小肠长度明显缩短(

0.05)，病理显示TPN组小鼠的小肠黏膜损伤明显，Chiu评分升高；血清肠屏障功能指标FITC、iFABP和肠组织炎症因子TNF-α、IL-1β水平高明显升高(

0.05)，肠道AhR活化指标CYP1A1，肠屏障紧密连接蛋白Zo-1、Occludin和肠组织抗炎因子IL-10水平明显降低(

0.05)。与TPN组比较，FICZ干预后小鼠体质量下降和小肠缩短程度明显降低(

0.05)，小肠黏膜损伤改善，Chiu评分降低(

0.05)；血清FITC、iFABP和肠组织TNF-α、IL-1β水平明显降低(

0.05)，肠组织CYP1A1、Zo-1、Occludin和IL-10水平明显升高(

0.05)。

结论

FICZ可通过AhR活化缓解肠黏膜炎症、调控紧密连接蛋白表达来减轻TPN引起的小鼠肠屏障损伤。

Abstract

Objective

To investigate the protective effects of aryl hydrocarbon receptor (AhR) activation of 6-formylindolo [3

2-B] carbazole (FICZ) on intestinal barrier damage and its potential mechanism in a mouse model of total parenteral nutrition (TPN).

Methods

TPN model was established in 18 mice with fluid infusion

via

external jugular vein

and then the mice randomly divided into control

TPN and TPN+FICZ (1 μg/d) groups. The mice of the TPN group and the TPN+FICZ group were infused with TPN solution and FICZ

those in the control group were treated with same amount of normal saline

and the mice of control group were allowed to eat freely. Their body weight were observed before and in 7 d after catheterization

and peripheral blood sample were harvested to detect intestinal barrier markers. All mice were sacrificed on day 7

and the terminal tissue of ileum was retained to detect protein and RNA expression of relevant molecules and observe the morphological changes of intestinal mucosa.

Results

After 7 d

when compared with the mice of the control group

the mice in the TPN group showed significantly decreased body weight

shorter length of small intestine (

0.05)

obvious mucosal damages in t

he intestine

higher Chiu score

increased serum levels of FITC and iFABP (intestinal barrier function indicators)

and enhanced expression levels of TNF-α and IL-1β (

0.05)

but obviously decreased level of CYP1A1 (an indicator of intestinal AhR activation)

and the levels of intestinal barrier tight junction proteins Zo-1 and Occludin and anti-inflammatory factor IL-10 in intestinal tissue (

0.05). While

FICZ intervention attenuated above changes in body weight and intestinal length (

0.05)

improved mucosal damage

reduced Chiu score (

0.05)

declined serum levels of FITC and iFABP and the levels of TNF-α and IL-1β in intestinal tissue (

0.05)

and up-regulated the expression levels of CYP1A1

Zo-1

Occludin and IL-10 (

0.05).

Conclusion

FICZ attenuates TPN-induced intestinal barrier damage in mice through AhR activation to relieve inflammation of intestinal mucosa and regulate expression of tight junction proteins.

关键词

Keywords

references

JAIN A K, WEN J X, ARORA S, et al . Validating hyperbilirubinemia and gut mucosal atrophy with a novel ultramobile ambulatory total parenteral nutrition piglet model[J ] . Nutr Res, 2015, 35(2): 169-174. DOI: 10.1016/j.nutres.2014.12.004.

DENTON C, PRICE A, FRIEND J, et al . Role of the gut-liver axis in driving parenteral nutrition-associated injury[J ] . Children, 2018, 5(10): 136. DOI: 10.3390/children5100136.

DREESEN M, FOULON V, SPRIET I, et al . Epidemiology of catheter-related infections in adult patients receiving home parenteral nutrition: a systematic review[J ] . Clin Nutr, 2013, 32(1): 16-26. DOI: 10.1016/j.clnu.2012.08.004.

ALVERDY J C, AOYS E, MOSS G S. Total parenteral nutrition promotes bacterial translocation from the gut[J]. Surgery, 1988, 104(2): 185-190.

MADNAWAT H, WELU A L, GILBERT E J, et al . Mechanisms of parenteral nutrition-associated liver and gut injury[J ] . Nutr Clin Pract, 2020, 35(1): 63-71. DOI: 10.1002/ncp.10461.

MOURA-ALVES P, FAÉ K, HOUTHUYS E, et al . AhR sensing of bacterial pigments regulates antibacterial defence[J ] . Nature, 2014, 512(7515): 387-392. DOI: 10.1038/nature13684.

SUN M G, MA N, HE T, et al . Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR)[J ] . Crit Rev Food Sci Nutr, 2020, 60(10): 1760-1768. DOI: 10.1080/10408398.2019.1598334..

WANG H, WEI Y B, YU D. Control of lymphocyte homeostasis and effector function by the aryl hydrocarbon receptor[J]. Int Immunopharmacol, 2015, 28(2): 818-824. DOI: 10.1016/j.intimp.2015.03.046.

GENEROSO S V, VIANA M L, SANTOS R G, et al . Protection against increased intestinal permeability and bacterial translocation induced by intestinal obstruction in mice treated with viable and he at-killed Saccharomyces boulardii[J ] . Eur J Nutr, 2011, 50(4): 261-269. DOI: 10.1007/s00394-010-0134-7.

XIAO W D, FENG Y J, HOLST J J, et al . Glutamate prevents intestinal atrophy via luminal nutrient sensing in a mouse model of total parenteral nutrition[J ] . FASEB J, 2014, 28(5): 2073-2087. DOI: 10.1096/fj.13-238311..

DENG G F, LEI Q C, GAO X J, et al . Glucagon-like peptide-2 modulates enteric paneth cells immune response and alleviates gut inflammation during intravenous fluid infusion in mice with a central catheter[J ] . Front Nutr, 2021, 8: 688715. DOI: 10.3389/fnut.2021.688715.

BUSCH R A, HENEGHAN A F, PIERRE J F, et al . The enteric nervous system neuropeptide, bombesin, reverses innate immune impairments during parenteral nutrition[J ] . Ann Surg, 2014, 260(3): 432-443;discussion 443-444. DOI: 10.1097/SLA.0000000000000871.

CHEN L M, BAO C H, WU Y, et al . Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease[J ] . J Neuroinflam, 2021, 18(1): 135. DOI: 10.1186/s12974-021-02175-2.

WANG J W, TIAN F, WANG P, et al . Gut microbiota as a modulator of paneth cells during parenteral nutrition in mice[J ] . J Parenter Enteral Nutr, 2018, 42(8): 1280-1287. DOI: 10.1002/jpen.1162.

LAMAS B, RICHARD M L, LEDUCQ V, et al . CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands[J ] . Nat Med, 2016, 22(6): 598-605. DOI: 10.1038/nm.4102.

APETOH L, QUINTANA F J, POT C, et al . The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27[J ] . Nat Immunol, 2010, 11(9): 854-861. DOI: 10.1038/ni.1912.

EKELUND M, KRISTENSSON E, EKELUND M, et al . Total parenteral nutrition causes circumferential intestinal atrophy, remodeling of the intestinal wall, and redistribution of eosinophils in the rat gastrointestinal tract[J ] . Dig Dis Sci, 2007, 52(8): 1833-1839. DOI: 10.1007/s10620-006-9678-z.

FREEMAN J J, FENG Y, BROWNER P J, et al . TPN-associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways[J ] . J Surg Res, 2014, 186(2): 621. DOI: 10.1016/j.jss.2013.11.617.

WANG Q M, YANG K Q, HAN B, et al . Aryl hydrocarbon receptor inhibits inflammation in DSS-induced colitis via the MK2/p-MK2/TTP pathway[J ] . Int J Mol Med, 2018, 41(2): 868-876. DOI: 10.3892/ijmm.2017.3262..

FENG Y J, SUN X Y, YANG H, et al . Dissociation of E-cadherin and beta-catenin in a mouse model of total parenteral nutrition: a mechanism for the loss of epithelial cell proliferation and villus atrophy[J ] . J Physiol, 2009, 587(3): 641-654. DOI: 10.1113/jphysiol.2008.162719.

GONG S Y, ZHENG J C, ZHANG J J, et al . Taxifolin ameliorates lipopolysaccharide-induced intestinal epithelial barrier dysfunction via attenuating NF-kappa B/MLCK pathway in a Caco-2 cell monolayer model[J ] . Food Res Int, 2022, 158: 111502. DOI: 10.1016/j.foodres.2022.111502..

HAN B, SHENG B F, ZHANG Z C, et al . Aryl hydrocarbon receptor activation in intestinal obstruction ameliorates intestinal barrier dysfunction via suppression of MLCK-MLC phosphorylation pathway[J ] . Shock, 2016, 46(3): 319-328. DOI: 10. 1097/SHK. 0000000000000594..

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