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  • Title: Breakdown of intestinal mucosa via accelerated apoptosis increases intestinal permeability in experimental severe acute pancreatitis.
    Author: Yasuda T, Takeyama Y, Ueda T, Shinzeki M, Sawa H, Nakajima T, Kuroda Y.
    Journal: J Surg Res; 2006 Sep; 135(1):18-26. PubMed ID: 16603187.
    Abstract:
    BACKGROUND: Bacterial translocation plays an important role for infectious complications in severe acute pancreatitis (SAP). Breakdown of intestinal mucosal integrity may increase intestinal permeability and may be implicated in bacterial translocation. It is suggested that increase in intestinal permeability is correlated with the changes of tight junction and/or apoptosis in intestinal epithelial cells. The aim of this study was to investigate the changes of intestinal mucosa and its permeability in SAP. METHODS: SAP was induced by injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats. Permeability of intestinal wall was assayed ex vivo by measuring the leaked amount of FITC-dextran from the ileum pouch. Alteration of tight junction proteins such as zonula occludens (ZO)-1 and Occludin was evaluated by Western blotting and immunofluorescence staining. Apoptotic change of intestinal mucosa was detected by TUNEL staining and DNA fragmentation ELISA. In vitro, apoptosis-inducing effect of pancreatitis-associated ascitic fluid (PAAF) was examined using T84 cells. Integrity of monolayer cells was assessed by transepithelial electric resistance (TEER). RESULTS: Permeability of ileum was significantly increased 6 h after induction of SAP. Blood endotoxin level was significantly elevated and bacterial translocation occurred 18 h after induction of SAP. Six hours after induction of SAP, expressions of ZO-1 and Occludin were not altered, but apoptosis of ileum mucosa was significantly accelerated. Addition of PAAF to T84 cells did not affect expressions of ZO-1 or Occludin, but significantly increased the apoptosis and significantly decreased TEER. CONCLUSIONS: These results suggest that breakdown of intestinal mucosa via accelerated apoptosis may increase in intestinal permeability in SAP and that PAAF contains factor(s) that accelerates the apoptosis of intestinal epithelial cells.
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