食品添加剂羧甲基纤维素钠通过破坏肠内环境加剧辐射对小鼠肠道的损伤

刘绍庭; 李忠俊; 陈立; 向阳; 相丽欣; 张薇薇; 冉茜; 王建

doi:10.16016/j.2097-0927.202310094

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食品添加剂羧甲基纤维素钠通过破坏肠内环境加剧辐射对小鼠肠道的损伤

基础医学 | 更新时间：2026-01-09

- 食品添加剂羧甲基纤维素钠通过破坏肠内环境加剧辐射对小鼠肠道的损伤
- Food additive sodium carboxymethyl cellulose aggravates radiation-induced intestinal damage in mice by disrupting intestinal homeostasis
- 陆军军医大学学报 2024年46卷第6期页码：522-534
- 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: 输血科
- 作者简介：
  
  [冉茜, E-mail: louise-r-q@163.comRAN Qian, E-mail: louise-r-q@163.com
  [王建, E-mail: wangjian_1996@aliyun.com WANG Jian, E-mail: wangjian_1996@aliyun.com
- 基金信息：
  
  重庆市杰出青年基金(CSTC2021jcyj-jqx0004);国家自然科学基金面上项目(81972973)
- DOI：10.16016/j.2097-0927.202310094
  中图分类号： R322.45;R339.57;TS202.3
- 收稿：2023-10-25，
  
  修回：2024-01-18，
  
  纸质出版：2024-03-30
- 稿件说明：
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刘绍庭, 李忠俊, 陈立, 等. 食品添加剂羧甲基纤维素钠通过破坏肠内环境加剧辐射对小鼠肠道的损伤[J]. 陆军军医大学学报, 2024,46(6):522-534.

Shaoting LIU, Zhongjun LI, li CHEN, et al. Food additive sodium carboxymethyl cellulose aggravates radiation-induced intestinal damage in mice by disrupting intestinal homeostasis[J]. Journal of Army Medical University, 2024, 46(6): 522-534.
刘绍庭, 李忠俊, 陈立, 等. 食品添加剂羧甲基纤维素钠通过破坏肠内环境加剧辐射对小鼠肠道的损伤[J]. 陆军军医大学学报, 2024,46(6):522-534. DOI： 10.16016/j.2097-0927.202310094.

Shaoting LIU, Zhongjun LI, li CHEN, et al. Food additive sodium carboxymethyl cellulose aggravates radiation-induced intestinal damage in mice by disrupting intestinal homeostasis[J]. Journal of Army Medical University, 2024, 46(6): 522-534. DOI： 10.16016/j.2097-0927.202310094.

摘要

目的

探究食品添加剂羧甲基纤维素钠(CMC-Na)的长期摄入对小鼠辐射耐受性的影响及其机制研究。

方法

通过饲饮水中添加不同浓度CMC-Na(对照组，0.25%低剂量组，1%高剂量组)对小鼠进行饮食干预，而后建立辐射损伤模型(7 Gy，Co

γ射线)。在辐射干预前后，每周称量小鼠体质量变化，记录各组小鼠的死亡情况；干预8周后，检测血生化指标；ELISA、RT-qPCR和Western blot技术检测肠道相关细胞因子和蛋白变化情况；HE、免疫荧光及免疫组化染色切片观察肠道组织细胞形态的改变并进行病理评分；流式细胞术检测肠道干细胞比例。

结果

通过流式细胞术检测发现，与对照组比较，两组饮食干预组的肠道干细胞比例均出现下降(

0.05)，下降程度与饮水中添加剂浓度呈正相关，且干细胞下降趋势在受到辐射损伤后持续存在。其中高剂量组死亡率显著升高(

0.05)，体质量大幅下降(

0.000 1)。进一步实验发现肠道屏障功能受损，抑炎因子白介素-10(IL-10)含量下降。同时，高剂量组小鼠肠道中出现了TLR4、NF-κB、TNF-α以及IL-1β等炎症因子的高表达(

0.05)，并且在辐射损伤后进一步加剧；低剂量组小鼠部分炎症因子(NF-κB、TNF-α以及IL-1β)相较于对照组表达增高(

0.05)，但低于高剂量组。

结论

长期摄入含有CMC-Na添加剂的饮食，会降低肠道内干细胞群的比例，加剧了辐射对肠道的损伤，降低了小鼠对辐射耐受性。

Abstract

Objective

To explore the effect and underlying mechanism of long-term intake of sodium carboxymethyl cellulose (CMC-Na)

a food additive

on radiation tolerance in mice.

Methods

Dietary inte

rvention was performed on the mice by adding different concentrations of CMC-Na to drinking water at a dose of 0

0.25% and 1%

respectively (Control and low-and high-dose groups) for 8 weeks

and then the mice were given a lethal radiation of 7 Gy

Co gamma rays to establish a radiation damage model. Before and after the radiation intervention

the body weight was measured weekly in every mice

and death was observed and recorded in each group. After an 8-week intervention

the blood biochemical indicators of mice were assessed. ELISA

Qrt-Pcr

and Western blotting techniques to investigate changes in intestinal-related cytokines and proteins. What's more

HE staining

immunofluorescence assay and immunohistochemical staining were used to observe the changes of intestinal tissue morphology for pathological scores. Flow cytometry was employed to detect the proportion of intestinal stem cells.

Results

Flow cytometry showed that the proportion of intestinal stem cells was decreased in both dietary intervention groups when compared with the control group (

0.05)

and the decrease was positively correlated with the dose of CMC-Na in drinking water and persisted after radiation damage. Higher death rate (

0.05) and obvious weight loss (

0.000 1) were observed in the high-dose intervention group

and impaired intestinal barrier function and a decrease in the content of the anti-inflammatory factor IL-10 were found in further research. Meanwhile

the expression levels of inflammatory factors such as TLR4

NF-κB

TNF-α and IL-1β were higher in the high-dose intervention group (

0.05)

and the contents were further increased after radiation damage. The expression of certain inflammatory factors (NF-κB

TNF-α

and IL-1β) in the low-dose group exhibited a statistically significant increase compared to the control group (

0.05)

yet remained lower than that observed in

the high-dose group.

Conclusion

Long-term consumption of foods containing CMC-Na reduces the proportion of colonic stem cells in the intestinal tract

aggravates the radiation damage to the intestine

and reduces the radiation tolerance of mice.

关键词

Keywords

references

李玉岭, 毛欣, 张元帅, 等. 辐射诱变技术在木本植物育种中的应用及展望[J]. 生物技术通报, 2023, 39(6): 12-30. DOI: 10.13560/j.cnki.biotech.bull.1985.2022-1008.

LI Y L, MAO X, ZHANG Y S, et al . Applications and perspectives of radiation mutagenesis in woody plant breeding[J ] . Biotechnol Bull, 2023, 39(6): 12-30. DOI: 10.13560/j.cnki.biotech.bull.1985.2022-1008.

周信宏, 黄钢. PET-CT多模态融合在图像语义分割的应用进展[J]. 中国医学物理学杂志, 2023, 40(6): 683-694. DOI: 10.3969/j.issn.1005-202X.2023.06.004.

ZHOU X H, HUANG G. Multimodal fusion of PET-CT for semantic image segmentation: a review[J]. Chin J Med Phys, 2023, 40(6): 683-694. DOI: 10.3969/j.issn.1005-202X.2023.06.004.

李珅, 辛军. PET/CT预测非小细胞肺癌EGFR突变与靶向治疗疗效的研究进展[J]. 中国临床医学影像杂志, 2023, 34(6): 437-440. DOI: 10.12117/jccmi.2023.06.012.

LI S, XIN J. Current progress for predicting EGFR mutations in patients with non-small cell lung cancer and exploring the efficacy of targeted therapy using of PET/CT images[J]. J China Clin Med Imag, 2023, 34(6): 437-440. DOI: 10.12117/jccmi.2023.06.012.

SUZUKI K, YAMASHITA S. Radiation-induced bystander response: mechanism and clinical implications[J]. Adv Wound Care, 2014, 3(1): 16-24. DOI: 10.1089/wound.2013.0468.

PARRISH J S, SEDA G. Disasters resulting from radiologic and nuclear events[J]. Crit Care Clin, 2019, 35(4): 619-631. DOI: 10.1016/j.ccc.2019.06.005.

COX S, SANDALL A, SMITH L, et al . Food additive emulsifiers: a review of their role in foods, legislation and classifications, presence in food supply, dietary exposure, and safety assessment[J ] . Nutr Rev, 2021, 79(6): 726-741. DOI: 10.1093/nutrit/nuaa038.

SHAH R, KOLANOS R, DINOVI M J, et al . Dietary exposures for the safety assessment of seven emulsifiers commonly added to foods in the United States and implications for safety[J ] . Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2017, 34(6): 905-917. DOI: 10.1080/19440049.2017.1311420.

OGULUR I, YAZICI D, PAT Y, et al . Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80[J ] . Allergy, 2023, 78(9): 2441-2455. DOI: 10.1111/all.15825.

CHASSAING B, KOREN O, GOODRICH J K, et al . Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome[J ] . Nature, 2015, 519(7541): 92-96. DOI: 10.1038/nature14232.

LI Y, XIAO H W, DONG J L, et al . Gut microbiota metabolite fights against dietary polysorbate 80-aggravated radiation enteritis[J ] . Front Microbiol, 2020, 11: 1450. DOI: 10.3389/fmicb.2020.01450.

CHASSAING B, COMPHER C, BONHOMME B, et al . Randomized controlled-feeding study of dietary emulsifier carboxymethylcellulose reveals detrimental impacts on the gut microbiota and metabolome[J ] . Gastroenterology, 2022, 162(3): 743-756. DOI: 10.1053/j.gastro.2021.11.006.

ZANGARA M T, PONTI A K, MILLER N D, et al . Maltodextrin consumption impairs the intestinal mucus barrier and accelerates colitis through direct actions on the epithelium[J ] . Front Immunol, 2022, 13: 841188. DOI: 10.3389/fimmu.2022.841188.

FURUHASHI H, HIGASHIYAMA M, OKADA Y, et al . Dietary emulsifier polysorbate-80-induced small-intestinalvulnerability to indomethacin-induced lesions via dysbiosis[J ] . J Gastroenterol Hepatol, 2020, 35(1): 110-117. DOI: 10.1111/jgh.14808.

LAUDISI F, DI FUSCO D, DINALLO V, et al . The food additive maltodextrin promotes endoplasmic reticulum stress-driven mucus depletion and exacerbates intestinal inflammation[J ] . Cell Mol Gastroenterol Hepatol, 2019, 7(2): 457-473. DOI: 10.1016/j.jcmgh.2018.09.002.

牛生洋, 郝峰鸽. 羧甲基纤维素钠的应用进展[J]. 安徽农业科学, 2006, 34(15): 3574-3575. DOI: 10.13989/j.cnki.0517-6611.2006.15.005.

NIU S Y, HAO F G. Application progress of sodium carboxymethyl cellulose[J]. J Anhui Agric Sci, 2006, 34(15): 3574-3575. DOI: 10.13989/j.cnki.0517-6611.2006.15.005.

Organization W H, Nations F A A O. The Codex General Standard for Food Additives[S]. Ccfa, 2019.

China N H C O. National standards for food safety. Standards for the use of food additives[S]. China T C O S, 2015.

KORDAHI M C, DELAROQUE C, BREDÈCHE M F, et al . Vaccination against microbiota motility protects mice from the detrimental impact of dietary emulsifier consumption[J ] . PLoS Biol, 2023, 21(9): e3002289. DOI: 10.1371/journal.pbio.3002289.

CHASSAING B, VAN DE WIELE T, DE BODT J, et al . Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation[J ] . Gut, 2017, 66(8): 1414-1427. DOI: 10.1136/gutjnl-2016-313099..

ROBERTS C L, KEITA A V, DUNCAN S H, et al . Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers[J ] . Gut, 2010, 59(10): 1331-1339. DOI: 10.1136/gut.2009.195370..

ROUSTA E, OKA A, LIU B, et al . The emulsifier carboxymethylcellulose induces more aggressive colitis in humanized mice with inflammatory bowel disease microbiota than polysorbate-80[J ] . Nutrients, 2021, 13(10): 3565. DOI: 10.3390/nu13103565.

VIENNOIS E, BRETIN A, DUBÉ P E, et al . Dietary emulsifiers directly impact adherent-invasive E . coli gene expression to drive chronic intestinal inflammation[J ] . Cell Rep, 2020, 33(1): 108229. DOI: 10.1016/j.celrep.2020.108229..

HARUSATO A, CHASSAING B, DAURIAT C J G, et al . Dietary emulsifiers exacerbate food allergy and colonic type 2 immune response through microbiota modulation[J ] . Nutrients, 2022, 14(23): 4983. DOI: 10.3390/nu14234983.

HAN Y Y, LIU L Y, CHEN Y Q, et al . Qing Hua Chang Yin alleviates chronic colitis of mice by protecting intestinal barrier function and improving colonic microflora[J ] . Front Pharmacol, 2023, 14: 1176579. DOI: 10.3389/fphar.2023.1176579..

ROLHION N, DARFEUILLE-MICHAUD A. Adherent-invasive Escherichia coli in inflammatory bowel disease[J ] . Inflamm Bowel Dis,2007, 13(10): 1277-1283. DOI: 10.1002/ibd.20176.

BEUMER J, CLEVERS H. Cell fate specification and differentiation in the adult mammalian intestine[J]. Nat Rev Mol Cell Biol, 2021, 22(1): 39-53. DOI: 10.1038/s41580-020-0278-0.

GEHART H, CLEVERS H. Tales from the crypt: new insights into intestinal stem cells[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(1): 19-34. DOI: 10.1038/s41575-018-0081-y.

WANG F C, SCOVILLE D, HE X C, et al . Isolation and characterization of intestinal stem cells based on surface marker combinations and colony-formation assay[J ] . Gastroenterology, 2013, 145(2): 383-395. e1-21. DOI: 10.1053/j.gastro.2013.04.050.

TAN S H, PHUAH P, TAN L T, et al . A constant pool of Lgr5 + intestinal stem cells is required for intestinal h omeostasis[J ] . Cell Rep, 2021, 34(4): 108633. DOI: 10.1016/j.celrep.2020.108633..

徐宝财, 王瑞, 张桂菊, 等. 国内外食品乳化剂研究现状与发展趋势[J]. 食品科学技术学报, 2017, 35(4): 1-7. DOI: 10.3969/j.issn.2095-6002.2017.04.001.

XU B C, WANG R, ZHANG G J, et al . Research progress and prospect in food emulsifiers[J ] . J Food Sci Technol, 2017, 35(4): 1-7. DOI: 10.3969/j.issn.2095-6002.2017.04.001.

BARKER N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration[J]. Nat Rev Mol Cell Biol, 2014, 15(1): 19-33. DOI: 10.1038/nrm3721.

ZHU Y, CAI P J, DAI H C, et al . Black chokeberry ( Aronia melanocarpa L. ) polyphenols attenuate obesity-induced colonic inflammation by regulating gut microbiota and the TLR4/NF-κB signaling pathway in high fat diet-fed rats[J ] . Food Funct, 2023, 14(22): 10014-10030. DOI: 10.1039/d3fo02177g..

ZHANG Y, ZHANG L, ZHENG S, et al . Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis[J ] . Gut Microbes, 2022, 14(1): 2038852. DOI: 10.1080/19490976.2022.2038852..

FRICK A, KHARE V, JIMENEZ K, et al . A novel PAK1-Notch1 axis regulates crypt homeostasis in intestinal inflammation[J ] . Cell Mol Gastroenterol Hepatol, 2021, 11(3): 892-907. e1. DOI: 10.1016/j.jcmgh.2020.11.001.

YAN S G, WANG P, WEI H L, et al . Treatment of ulcerative colitis with Wu-Mei-Wan by inhibiting intestinal inflammatory response and repairing damaged intestinal mucosa[J ] . Phytomedicine, 2022, 105: 154362. DOI: 10.1016/j.phymed.2022.154362.

SI X M, JIA H, LIU N, et al . Alpha-ketoglutarate attenuates colitis in mice by increasing Lactobacillus abundance and regulating stem cell proliferation via wnt-hippo signaling[J ] . Mol Nutr Food Res, 2022, 66(10): e2100955. DOI: 10.1002/mnfr.202100955..

ZHANG D S, TANG W J, NIU H T, et al . Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia[J ] . Genes Dis, 2023, 11(1): 413-429. DOI: 10.1016/j.gendis.2022.11.024.

张宇凤, 于冬梅, 赵丽云. 2010—2012年中国成年居民零食消费现状及影响因素[J]. 卫生研究, 2017, 46(2): 184-188. DOI: 10.19813/j.cnki.weishengyanjiu.2017.02.003.

ZHANG Y F, YU D M, ZHAO L Y. Snacking consumption and influencing factors among Chinese adults in 2010—2012[J]. J Hyg Res, 2017, 46(2): 184-188. DOI: 10.19813/j.cnki.weishengyanjiu.2017.02.003.

相林, 叶丽红, 张竞雯, 等. 中国六省份中小学生预包装食品购买行为及其影响因素分析[J]. 中华预防医学杂志, 2022, 56(11): 1604-1611. DOI: 10.3760/cma.j.cn112150-20211126-01090.

XIANG L, YE L H, ZHANG J W, et al . The purchase behavior of prepackaged food and its determinants among primary and middle school students in 6 provinces of China[J ] . Chin J Prev Med, 2022, 56(11): 1604-1611. DOI: 10.3760/cma.j.cn112150-20211126-01090.

王秀丽, 张颢城, 祝超然, 等. 北京市初中学生全食物消费现状研究[J]. 中国食物与营养, 2023, 29(4): 33-39. DOI: 10.19870/j.cnki.11-3716/ts.20221114.001.

WANG X L, ZHANG H C, ZHU C R, et al . Study on the current situation of total food consumption of junior middle school students in Beijing city[J ] . Food Nutr China, 2023, 29(4): 33-39. DOI: 10.19870/j.cnki.11-3716/ts.20221114.001.

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