Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice,
obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice
exclusion from gut exacerbates Akt/nuclear factor-
kB (NF-
kB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic
duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before
duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n=7/group).
Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-
kB (I-
kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates.
NF-
kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases
in pancreatic Akt, I
kB, and NF-
kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-
kB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic
juice replacement (ANOVA,
P<0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-
kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis.
Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster).
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