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昼夜节律的短暂紊乱会改变肠道屏障完整性,并调节小鼠中右旋葡聚糖硫酸钠(DSS)诱导的结肠炎严重程度。

Brief Disruption of Circadian Rhythms Alters Intestinal Barrier Integrity and Modulates DSS-Induced Colitis Severity in Mice.

作者信息

Barrios Bibiana E, Jaime Cristian E, Sena Angela A, de Paula-Silva Marina, Gil Cristiane D, Oliani Sonia M, Correa Silvia G

机构信息

Inmunología, Departamento de Bioquímica Clínica-CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.

Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.

出版信息

Inflammation. 2024 Oct 16. doi: 10.1007/s10753-024-02162-8.

DOI:10.1007/s10753-024-02162-8
PMID:39407037
Abstract

Physiological processes in organisms exhibit circadian rhythms that optimize fitness and anticipate environmental changes. Luminal signals such as food or metabolites synchronize bowel activity, and disruptions in these rhythms are linked to metabolic disorders and gastrointestinal inflammation. To characterize the intrinsic intestinal rhythms and assess disruptions due to continuous darkness or light exposure, C57BL/6 mice were exposed to standard light-dark conditions or continuous light/darkness for 48 h, with evaluations at four timepoints. We assessed intestinal morphology, mucus production, nitric oxide levels and permeability. Under standard light: dark cycles, mice showed changes in intestinal morphology consistent with normal tract physiology. Continuous light exposure caused marked alterations in the small intestine´s epithelium and lamina propria, reduced nitric oxide production in the colon, and predominant neutral mucins. Enhanced permeability was indicated by higher FITC-dextran uptake and increased frequency of IgG-coated bacteria. Additionally, the 48 h-disruption influenced DSS-induced colitis with attenuation in L:L group, or exacerbation in D:D group, of clinical signs. These findings highlight the critical role of circadian rhythms in gut histoarchitecture and function, demonstrating that short-term disruptions in light-dark cycles can compromise intestinal barrier integrity and impact inflammatory outcomes.

摘要

生物体中的生理过程呈现出昼夜节律,这种节律能优化适应性并预测环境变化。诸如食物或代谢物等腔内信号会使肠道活动同步,而这些节律的紊乱与代谢紊乱和胃肠道炎症有关。为了表征肠道的内在节律,并评估持续黑暗或光照暴露所导致的节律紊乱,将C57BL/6小鼠置于标准明暗条件或持续光照/黑暗环境中48小时,并在四个时间点进行评估。我们评估了肠道形态、黏液分泌、一氧化氮水平和通透性。在标准明暗循环条件下,小鼠的肠道形态变化与正常肠道生理状况一致。持续光照暴露导致小肠上皮和固有层出现明显改变,结肠中一氧化氮生成减少,中性黏蛋白占主导。较高的异硫氰酸荧光素 - 葡聚糖摄取量和IgG包被细菌频率增加表明通透性增强。此外,48小时的节律紊乱对葡聚糖硫酸钠(DSS)诱导的结肠炎产生影响,在持续光照组(L:L)中临床症状减轻,而在持续黑暗组(D:D)中临床症状加重。这些发现突出了昼夜节律在肠道组织结构和功能中的关键作用,表明明暗循环的短期紊乱会损害肠道屏障完整性并影响炎症结果。

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本文引用的文献

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Mol Cell Biochem. 2023 Mar;478(3):581-595. doi: 10.1007/s11010-022-04536-8. Epub 2022 Aug 17.
2
Luminal bacteria coated with IgA and IgG during intestinal inflammation as a new and abundant stimulus for colonic macrophages.在肠道炎症期间,黏附在 IgA 和 IgG 上的腔菌成为结肠巨噬细胞的一种新的、丰富的刺激物。
Immunology. 2022 Sep;167(1):64-76. doi: 10.1111/imm.13518. Epub 2022 Jun 25.
3
A High-Fat Western Diet Attenuates Intestinal Changes in Mice with DSS-Induced Low-Grade Inflammation.
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J Nutr. 2022 Mar 3;152(3):758-769. doi: 10.1093/jn/nxab401.
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Photobiomodulation Enhances the Angiogenic Effect of Mesenchymal Stem Cells to Mitigate Radiation-Induced Enteropathy.光生物调节增强间充质干细胞的血管生成作用,以减轻放射性肠炎。
Int J Mol Sci. 2019 Mar 5;20(5):1131. doi: 10.3390/ijms20051131.
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An In Vivo Method to Study Mouse Blood-Testis Barrier Integrity.一种研究小鼠血睾屏障完整性的体内方法。
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