Splenectomy Attenuates Severe Thermal Trauma-induced Intestinal Barrier Breakdown in Rats  

作　　者：柳向东 陈振勇 杨鹏 黄文广 蒋春舫 

机构地区：[1]Department of Plastic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University [2]Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2015年第6期868-873,共6页华中科技大学学报（医学英德文版）

基　　金：supported by the Natural Science Foundation of Hubei Province(No.2010CDBO7804)

摘　　要：Summary： 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 （T J） is highly regulated by membrane-associated proteins including zonula occludens protein-1 （ZO-1） and oc- cludin, 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 perme- ability, 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 in- jury 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 bum caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the av- erage 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）. Sple- nectomy at 7th day after burn significantly reversed the bum-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 bum-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.Summary： 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 （T J） is highly regulated by membrane-associated proteins including zonula occludens protein-1 （ZO-1） and oc- cludin, 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 perme- ability, 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 in- jury 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 bum caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the av- erage 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）. Sple- nectomy at 7th day after burn significantly reversed the bum-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 bum-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.

关 键 词：BURN SPLENECTOMY ENDOTOXIN nuclear factor-κB tumor necrosis factor-alpha zonula oc-cludens protein- 1 OCCLUDIN 

分 类 号：R657.6[医药卫生—外科学]