Effect of extracellular histones on intestinal mucosa barrier function in mice and role of extracellular histones in development of sepsis
10.3760/cma.j.issn.1001-8050.2016.10.004
- VernacularTitle:细胞外组蛋白对损伤小鼠肠黏膜屏障的影响及在脓毒症发生发展中的作用
- Author:
Xin WANG
;
Song WU
;
Shuyun ZHENG
;
Shoutao YUAN
;
Xiang WANG
;
Shangyu CHEN
;
Zhenling JI
- Publication Type:Journal Article
- Keywords:
Histones;
Intestines;
Sepsis
- From:
Chinese Journal of Trauma
2016;32(10):882-886
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of extracellular histones (EH) on intestinal mucosal barrier function in mice and the correlation of EH with the pathogenesis of sepsis.Methods Twenty male C57BL/6 mice were assigned into experiment group (n =10) and control group (n =10) according to the random number table.Same dose (50 mg/kg) of EH and saline were administered through the caudal vein of mice in experiment and control groups respectively.Blood and intestinal samples in each group were collected 3 h after the administration.Morphology of intestinal mucosal tissue was detected by light scope and transmission electron microscope.Expressions of tight junction related proteins (ZO-1,Occludin and Claudin-1) were detected by western blot.Plasma levels of diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) were determined by ELISA method.Plasma level of endotoxin (ET) was determined by limulus test.Results Under transmission electron microscope,experiment group showed disorganized microvilli of intestinal epithelial cells with partially twisted,broken and lost,unclear tight junctions,and widened cellular space.Under light scope,experiment group showed substantial inflammatory cell infiltration in the intestinal wall,disorganized intestinal villi,edema and hemorrhage of mucosa and submucosa,and edematous goblet cells.Experimental versus control group showed significant reduction in levels of Claudin-1 (0.587 7 ±0.060 6 vs.0.677 2 ±0.038 3),Occludin (0.1277±0.0857vs.0.4306±0.0869) and ZO-1 (0.393 3±0.080 8 vs.0.812 8± 0.096 3) (P ＜ 0.05).Experimental versus control group showed significantly up-regulated plasma levels of DAO [(1.61 ±0.20) U/ml vs.(0.69 ± 0.15) U/ml],I-FABP [(548.5 ± 36.8) EU/ml vs.(178.8±26.9) EU/ml] andET [(0.182±0.076) EU/mlvs.(0.091 ±0.029) EU/ml](P＜0.05).Conclusion EH can obviously impair the integrity of intestinal mucosal barrier in mice and hence induce endotoxin translocation.
