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Am J Physiol Regul Integr Comp Physiol (July 18, 2002). doi:10.1152/ajpregu.00278.2002
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Articles in PresS, published online ahead of print July 18, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00278.2002
Submitted on May 16, 2002
Accepted on July 9, 2002

Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice

Runkuan Yang1, David J Gallo2, Jeffrey J Baust2, Simon K Watkins3, Russell L Delude4, and Mitchell P Fink5*

1 Departments of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2 Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3 Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Departments of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
5 Departments of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: finkmp{at}anes.upmc.edu.

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 fluorescein isothiocyanate dextran and hepatic and ileal mucosal steady-state IL-6, iNOS, 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 pro-inflammatory 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 up-regulated 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.




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