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

作者：Ouyang, Jun; Zhang, Zhao-hui; Zhou, Yue-xian; Niu, Wan-cheng; Zhou, Feng; Shen, Chang-bing; Chen, Ren-guo; Li, Xi^*

来源：Pancreas, 2016, 45(8): 1136-1144.

DOI：10.1097/MPA.0000000000000656

• severe acute pancreatitis
• p38 mitogen-activated protein kinase
• p53
• tight junction
• ZO-1
• occludin

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 a, 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.

• 出版日期2016-9
• 单位上海交通大学; 徐州医科大学