Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis

Abstract

To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality, ascite volumes, ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3, 6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-alpha), phospholipase A(2) (PLA(2)) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared, terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-alpha, PLA(2) and IL-6 in serum, ascite volumes, ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points [P < 0.05, 58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-alpha content, 8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01, 0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content, 7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content, 1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio, 8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001, 3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content, 4.50 (2.00) vs 7.20 (2.00), 4.20 (1.60) vs 6.40 (2.30), 3.40 (2.70) vs 7.90 (1.70) in ascite volumes, respectively]. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h [P < 0.01, 0.00 (2.00)% vs 0.00 (0.00)%, 0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes, respectively]. The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.