Effect of SB203580 on pathologic change of pancreatic tissue and expression of TNF-α and IL-1β in rats with severe acute pancreatitis.

OBJECTIVE: This study aimed to investigate the effect of SB203580 which is the inhibitor of p38 mitogen-activated protein kinase on pathologic change of pancreatic tissue and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1b) in rats with severe acute pancreatitis (SAP), Hematoxylin-eosin (HE) staining and immunohistochemistry were carried out in the present study.

METHODS: Forty-five male Wistar rats were divided into three groups: the SAP group (N=15), SB203580-treated group (SB group) (N=15), and the control group (N=15). Severe acute pancreatitis was induced by injection of sodium taurocholate into the pancreatic duct. For SB203580-treated group, SB203580 were administered via intraperitoneal injection (10 mg/kg). Serum amylase activity was measured 6, 12 and 24 hours respectively after the operation. The pancreas tissue were stained with HE for histopathological evaluation and the expression of TNF-α and IL-1b in the pancreatic tissue were determined through inferior vena cava.

RESULTS: The results show that the level of amylase in SAP group was higher than that in the other groups. Further, the pancreas tissues of SB group rats were observed more mildly edematous, hemorrhagic and with monocytes infiltration. Based on immunohistochemical staining, the expression of TNF-α and IL-1β in SAP rats were significantly increased than those of the control group. However, those of SB203580-treated group were more significantly reduced than those of SAP group (p < 0.05).

CONCLUSIONS: Those data suggest that SB203580, down regulating the expression of pro-inflammatory mediators such as TNF-α and IL-1β, then through p38 MAPK signaling pathway inhibition, plays an important role in the treatment of SAP.