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Intestinal mucosal injury induced by obstructive jaundice is associated with activation of TLR4/TRAF6/NF-κB pathways


Autoři: Xiaopeng Tian aff001;  Huimin Zhao aff002;  Zixuan Zhang aff001;  Zengcai Guo aff002;  Wen Li aff001
Působiště autorů: Medical School of Chinese PLA, Beijing, China aff001;  Department of Gastroenterology, Xingtai People’s Hospital, Xingtai, Hebei, China aff002;  Department of Gastroenterology and Hepatology, the First Medical Center of Chinese PLA General Hospital, Beijing, China aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223651

Souhrn

Objectives

To investigate the role of TLR4/TRAF6/NF-κB pathways in intestinal mucosal injury induced by obstructive jaundice (OJ).

Methods

A total of 100 male C57BL/6J mice were randomly assigned to two groups: (I) sham operation (SH); (II) OJ. The mice were sacrificed before operation and on the 1st, 3rd, 5th and 7th day after operation. The blood and terminal ileum were simultaneously collected under the aseptic condition for further detection.

Results

In the SH group, TLR4 protein and mRNA rarely expressed in the intestinal mucosa of the mice and there were no significant differences at different time points (p>0.05). By contrast, in the OJ group TLR4 protein (0.12±0.06, 0.16±0.08, 0.27±0.10, 0.35±0.12 and 0.41±0.13, respectively) and mRNA (0.49±0.19, 0.62±0.23, 0.98±0.32, 1.42±0.41 and 1.72±0.49, respectively) increased gradually with the extension of time (p<0.05). Also in the OJ group, the levels of DAO and endotoxin in plasma as well as the expressions of NF-κB and caspase-3 increased gradually with the extension of time, showing positive correlation with the expression of TLR4 (p<0.05).

Conclusions

The expression of TLR4 was significantly up-regulated in the distal ileum of mice with OJ. Activation of the TLR4/TRAF6/NF-κB pathways was involved in the occurrence and development of intestinal mucosal injury and endotoxemia in mice with OJ.

Klíčová slova:

Apoptosis – Cytoplasm – Cytoplasmic staining – Endotoxins – Gastrointestinal tract – Ileum – Inflammation – Toll-like receptors


Zdroje

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