Dose-effect relationship and protective effect of MIF inhibitor on pancreas and placenta injuries in rats with acute necrotizing pancreatitis in late pregnancy

Objective To explore the protective effects and dose-effect relationship of ISO-1, a MIF inhibitor, on pancreatic and placental injuries in rats with acute necrotizing pancreatitis(ANP) in late pregnancy. Methods Thirty SD rats at late pregnancy were randomly(random number) divided into five groups(n=6 in each group): sham operation group(SO group), acute necrotizing pancreatitis group(ANP group) and ISO-1 pretreatment group in different dosages: T1 group(1.75 mg/kg), T2 group(3.5 mg/kg) and T3 group(7.0 mg/kg). ANP rat model was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. In ISO-1 pretreatment group, ISO-1 dissolved in 10% DMSO in different concentration was intra-peritoneal administered. The rats of SO group and ANP group were intra-peritoneal administered with 10%DMSO (2 mL/kg) 30 min before the ANP modeling. Rats were sacrificed 6 hours after modeling. The serum levels of amylase(AMY), lipase(LIP), alanine aminotransferase(ALT) and aspartate aminotransferase (AST) were detected by biochemical analyzer. Pancreatic and placental pathological changes were evaluated under the optics microscope. All data were analyzed by using the One-way analysis of variance(ANOVA) or student t test. Results The serum levels (U/L)of AMY, LIP, ALT and AST in ANP group were (7 101.4±1 032.3) , (2 939.0±638.8), (240.3±50.3) and (472.6±27.5), which were significantly higher than (2 268.7±293.8), (681.1±109.9), (56.4±15.3) and (110.9±15.5) of SO group (P 0.05). The pancreatic and placental pathological scores of the ANP group were(12.3±1.5)and(6.3±0.8), respectively, which were higher than (4.7±1.2) and (0.5±0.5) of SO group (P 0.05). Conclusion The peritoneal administration of MIF inhibitor probably has protective effect on the pancreatic and placental injury in late pregnancy rat with ANP. ISO-1 dosage in T2 group(3.5 mg/kg) is the optimal and safe dosage for attenuating pancreatic and placental injuries in rat model of ANP in late pregnancy. Key words: ISO-1; Pancreatitis; Pregnancy; Pancreas; Placenta; Dose-effect relationship