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Splenectomy attenuates severe thermal trauma-induced intestinal barrier breakdown in rats.

Abstract
The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all P<0.01). Splenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all P<0.01). The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.
AuthorsXiang-Dong Liu, Zhen-Yong Chen, Peng Yang, Wen-Guang Huang, Chun-Fang Jiang
JournalJournal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 35 Issue 6 Pg. 868-873 (Dec 2015) ISSN: 1993-1352 [Electronic] China
PMID26670438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Endotoxins
  • NF-kappa B
  • Occludin
  • Tjp1 protein, rat
  • Tumor Necrosis Factor-alpha
  • Zonula Occludens-1 Protein
Topics
  • Animals
  • Blotting, Western
  • Endotoxins (blood)
  • Female
  • Hot Temperature
  • Intestinal Mucosa (physiopathology)
  • Male
  • NF-kappa B (blood)
  • Occludin (metabolism)
  • Rats
  • Rats, Wistar
  • Splenectomy
  • Tumor Necrosis Factor-alpha (blood)
  • Zonula Occludens-1 Protein (metabolism)

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