title: Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice.
abstract: We sought to determine whether gut-derived microbial factors influence the hepatic or intestinal inflammatory response to hemorrhagic shock and resuscitation (HS/R). Conventional and gnotobiotic mice contaminated with a defined microbiota without gram-negative bacteria were subjected to either a sham procedure or HS/R. Tissue samples were obtained 4 h later for assessing ileal mucosal permeability to FITC dextran and hepatic and ileal mucosal steady-state IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF mRNA levels. Whereas HS/R significantly increased ileal mucosal permeability in conventional mice, this effect was not apparent in gnotobiotic animals. HS/R markedly increased hepatic mRNA levels for several proinflammatory genes in both conventional and gnotobiotic mice. HS/R increased ileal mucosal IL-6 and COX-2 mRNA expression in conventional but not gnotobiotic mice. If gnotobiotic mice were contaminated with Escherichia coli C25, HS/R increased ileal mucosal permeability and upregulated expression of IL-6 and COX-2. These data support the view that the hepatic inflammatory response to HS/R is largely independent of the presence of potentially pathogenic gram-negative bacteria colonizing the gut, whereas the local mucosal response to HS/R is profoundly influenced by the microbial ecology within the lumen during and shortly after the period of hemorrhage.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Runkuan
authors.initials: R
authors.lastname: Yang
authors.forename: David J
authors.initials: DJ
authors.lastname: Gallo
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Baust
authors.forename: Simon K
authors.initials: SK
authors.lastname: Watkins
authors.forename: Russell L
authors.initials: RL
authors.lastname: Delude
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D004064:Digestive System / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D019793:Fluorescein; D005753:Gastric Mucosa / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D005856:Germ-Free Life / Q000502:physiology*; D006090:Gram-Negative Bacteria; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000502:physiology; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010865:Pilot Projects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012151:Resuscitation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D013312:Stress, Physiological / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D015850:Interleukin-6; D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019793:Fluorescein