title: 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.
authors.affiliation: Department of Plastic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xhczy@126.com.
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004731:Endotoxins / Q000097:blood; D005260:Female; D006358:Hot Temperature; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008297:Male; D016328:NF-kappa B / Q000097:blood; D062793:Occludin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D004731:Endotoxins; D016328:NF-kappa B; D062793:Occludin; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein
keywords: burn; endotoxin; nuclear factor-κB; occludin; splenectomy; tumor necrosis factor-alpha; zonula occludens protein-1