Objective      To determine of the role of AMP-activated protein kinase (AMPK) in the damage of intestinal tight junction in the rats with severe acute pancreatitis.       Methods      The models of mild (MAP) and severe acute pancreatitis (SAP) were prepared by intraperitoneal injection of different doses of L-arginine solution (20%) to SD rats respectively

and then the models were confirmed by detection of serum amylase level and pathological changes of pancreatic tissues. The SAP rats were treated with the AMPK inhibitor

compound C

and glutamine respectively by gavage. The damages of small intestine mucosa were examined by pathological staining

and the intestinal permeability was measured by FITC-Dextran permeability assay. The expression of αSNAP

AMPK and tight junction protein (occludin) were detected by immunohistochemical assay and Western blot analysis.       Results      The rat models of MAP and SAP were successfully prepared

and inhibition of AMPK significantly attenuated the pathological changes of pancreatic tissues. Significant damage of small intestinal mucosa was observed in SAP rats

while compound C or glutamine markedly alleviated these damages. The intestinal permeability was significantly stronger in the SAP rats in 48 h after model establishment when compared to the control group (410.25±7.80 vs 0.51±0.61

P0.05)

while AMPK inhibitor

compound C (372.95±9.33) or glutamine (367.93±18.90) significantly inhibited the increased intestinal permeability in SAP rats (P0.05). In SAP rats

the expression level of αSNAP was decreased (P0.05)

while that of AMPK was increased obviously (P0.05). Inhibition of AMPK greatly enhanced the expression of occludin (P0.05)

suggesting a negative regulation between AMPK and occludin.       Conclusion      AMPK signal is over-activated in the damage of intestinal mucosa in SAP rats

and exerts negative modulation on occludin to induce the damage

and thus leads to increased intestinal permeability.