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Intestinal Barrier Dysfunction in Ageing Animals With Acute Pancreatitis: Increased Intestinal Inflammation?
Marcel C. Machado*1, Fabiano Pinheiro DA Silva1, Debora G. Cunha1, Denise F. Barbeiro1, ANA Maria M. Coelho2, Heraldo P. Souza1
1Emergency Medicine, University of Sao Paulo, Sao Paulo, Brazil; 2Gastroenterology, University of Sao Paulo, Sao Paulo, Brazil
Introduction/Background: Acute pancreatitis in elderly patients in spite of similar occurrence of local complications is followed by a substantial increase in morbidity and mortality rates with a significant financial impact. The mechanisms underlying this age related vulnerability remain unknown. Intestinal barriers dysfunction resulting in bacterial translocation from the intestinal lumen to distant organs has been incriminating as the main cause of infected necrotizing pancreatitis with increased mortality. The aim of the present study was to investigate if intestinal barrier dysfunction could be related to an increased intestinal inflammation in aged animals.
Methods: AP was induced in male Wistar rats by an intraductal 2.5% taurocholate injection and divided in 2 experimental groups (20 rats each group) G-1 young ( 3 month old rats) and G-2 older (18 month old rats). Twelve hours after AP fragments of distal ileum were collected for evaluation of the gene expression of Cycloxygenase-2(COX-2), and tight junction proteins (JAM-A and Occludin) and determination of inflammatory mediators (TNF and IL-10). Twenty four hours after AP induction pancreas tissue was collect in sterile conditions for bacterial culture.
Results: It was observed an increased bacterial translocation in the group of aged animals with AP (p< 0,05). We also observed an increase of intestinal Cox-2 gene expression in aged animals with AP when compared to young animals (p<0,05). It was also demonstrated an increased intestinal levels of TNF-alfa (p<0,0001) and decreased levels of IL-10 in aged animals when compared to young ones(p<0,0001) .We also observed an increased gene expression of tight junction proteins (JAM-A and Occludin) in young animal when compared to aged animals (p<0,005).
Conclusion: These results suggest that intestinal dysfunction in ageing animal with AP is related to increased intestinal inflammation and delay recovering of barrier breakdown. These results also suggest Cox 2 could be a potential target for reduction or prevention of barrier dysfunction in AP.
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