The effect of P38MAPK inhibitor on severe acute pancreatitis in rats

Abstract

Objective To explore the therapeutic effect of P38 mitogen-activated protein kinase (MAPK) inhibitor(SB203580) on severe acute pancreatitis(SAP). Methods Sixty-three Wistar rats were randomly allocated into three groups: sham operation group (group S), SAP group (group P),treatment group with SB203580 (group T). There were 21 rats in each group. Rat SAP model was induced by retrograde injection of 5% sodium taurocholate to pancreatic duct. After the model was successfully established, no treatments were given in group P. In group T, SB203580 ( 10 rmg/ml) was given by intraperitoneal injection(10 mg/kg). The rats in group S were only subjected to abdominal opening surgery. The rats were killed 1 h, 2 h and 4 h after operation. Serum levels of tumor necrosis factor-α (TNF-α) were measured by ELISA. The pancreas tissues were obtained to examine the changes with microscope, the expression of p-P38MAPK was examined by immunohistochemical technique and apoptosis of pancreatic acinar cells was detected by TUNEL methods. Results At the three time points, the levels of TNF-α and the activity of P38MAPK in group P andgroup T were significantly increased compared with those in group S ( P ＜0.05 ). In group T, the levels of TNF-α and the activity of P38MAPK were significantly decreased compared with those in group P(P＜0.05), the apoptosis rate of pancreatic acinar cell was significantly higher than those in group P ( P ＜ 0. 05 ). Pancreatic pathological damages were much milder in group T than those in group P under microscope. Conclusions P38MAPK plays an important role in the development of SAP. SB203580 can inhibit P38MAPK activity, decrease inflammatory mediator levels, increase the apoptosis rate of pancreatic acinar cell and reduce the pathological damage of the pancreas. Key words: P38 mitogen-activated protein kinase; Severe acute pancreatitis; Twnor necrosis factor; Apoptosis