Dose-Response Relationship of a Novel Phospholipase A_2 Inhibitor in Rat with Acute Hemorrhage Necrotizing Pancreatitis

Objective: To explore the dose-response relationship of a novel phospholipase A2 inhibitor in rat with acute hemorrhage necrotizing pancreatitis(AHNP).Methods: Sixty male Wistar rats were randomly allocated into five groups(n=12 for each group): sham operation group(SO group),acute hemorrhage necrotizing pancreatitis model group(AHNP group),and phospholipase A2 inhibitor pretreatment groups at different dosage(2.5,5,and 10 mg/kg).AHNP model was induced by retrograde infusion of 5 % sodium taurocholate(1 ml/kg) into the biliopancreatic duct.The rats of SO group and AHNP group were injected with 10%DMSO(2 ml/kg) by femoral vein 30 min before the operation.Phospholipase A2 inhibitor pretreatment groups were injected different dosage of a novel phospholipase A2 inhibitor instead of 10%DMSO.Rats were killed at 3 h and 12 h after operation.Blood samples were obtained for detecting serum amylase,alanine aminotransferase and creatinine.The samples of ascites were collected and measured.Pancreatic tissue samples were stained with hematoxylin and eosin for pancreatic histopathological evaluation.Results: The results of serum amylase,alanine aminotransferase,creatinine,ascites and pathologic score showed that they were significantly higher in AHNP group than those in SO group(P0.01),and were significantly lower in 5 and 10 mg/kg inhibitor pretreatment groups than those in AHNP group(P0.01) except the alanine aminotransferase in 5 mg/kg inhibitor pretreatment group,and there were no significantly difference between 2.5 mg/kg inhibitor group and AHNP group.All of the results except alanine aminotransferase and creatinine in 5 and 10 mg/kg inhibitor groups,which were not different from each other,were significantly higher than 2.5 mg/kg inhibitor group(P0.01).The results of alanine aminotransferase and creatinine in 10 mg/kg inhibitor group were significantly higher than those in 5 mg/kg group(P0.01).Conclusion: The novel phospholipase A2 inhibitor(5 mg/kg) administered intravenously was the optimal dosage for attenuating the severity of acute hemorrhage necrotizing pancreatitis induced by retrograde infusion sodium taurocholate.