Up-regulation of Tight-Junction Proteins by p38 Mitogen-Activated Protein Kinase/p53 Inhibition Leads to a Reduction of Injury to the Intestinal Mucosal Barrier in Severe Acute Pancreatitis.

ABSTRACT

OBJECTIVES: The aim of this study was to explore the role of the p38 mitogen-activated protein kinase (p38MAPK)/p53 signaling pathway in injury to the intestinal mucosal barrier during severe acute pancreatitis (SAP). METHODS: Both sham operation and SAP groups had 3 subgroups analyzed 3, 6, or 12 hours after the SAP induction. The concentrations of amylase, endotoxin, diamine oxidase, tumor necrosis factor α, and phospho-p38MAPK, p53, and caspase-3 and the messenger RNA levels of zonula occludens protein-1 and occludin in the intestine were measured. Immunohistochemical staining was used to determine the expression of zonula occludens protein-1 and occludin. Pathological changes of the pancreas and intestine were also assessed. Then, rats were randomly assigned to 5 groups-sham operation group, SAP group, 3 groups treated with different concentrations of p38MAPK-inhibitor SB203580-and the abovementioned experiment was repeated and analyzed 6 hours after the SAP induction. RESULTS: The phospho-p38MAPK reached a peak value at 6 hours after the SAP induction with obvious pathological injury to the pancreas and intestine. Treatment with SB203580 led to a less damage to the pancreatic and intestinal tissues. CONCLUSIONS: These results suggest that SAP activates the p38MAPK/p53 signaling pathway and induces injury to the intestinal mucosal barrier, which can be alleviated by inhibiting the p38MAPK/p53 pathway.