Research of dose-effect of 3-AB,a PARP Inhibitor on rats with severe acute pancreatitis

【Objective】To explore the dose -effect relationship of the PARP (poly -ADP ribose polymerase) inhibitor 3-aminobenzamide (3-AB) on rats with severe acute pancreatitis (SAP).【Methods】 Sixty SPF male Wistar rats were randomly allocated into six groups (n =10 for each group): sham operation group (SO group),severe acute pancreatitis model group (SAP group),3-AB pretreatment groups at different dosage (10,20 and 40 mg/kg),and drug control group (3-AB group).SAP model was induced by retrograde infusion of 5% sodium taurocholate (1 mL/kg) into the biliopancreatic duct.The rats of SO group and SAP group were injected with 5%DMSO (2 mL/kg) by femoral vein 30 min before the operation.3 -AB pretreatment groups were injected different dosage of 3 -AB dissolved in 5%DMSO,drug control group was chosen optimal dosage according to the effect of 3-AB.Rats in each group were sacrificed at 12 h after operation to measure the quantity of ascites,serum AMY,ALT and Cr and to observe the pathological changes of pancreatic tissues.【Results】 Compared with SO group,the results of ascites,serum AMY,ALT,Cr,and pancreatic pathologic score in SAP Group was all significantly increased (P 0.05).T1 group can reduce the quantity of ascites,but failed to decrease the index value of serum and pancreatic pathologic score;T3 group can reduce serum AMY,ALT,and pancreatic pathologic score,but failed to decrease the levels of ascites and serum Cr (P 0.05),while T2 group can significantly reduce the above-mentioned indicators (P 0.05).The difference of the above-mentioned indicators between Drug control group (20 mg/kg 3-AB) and SO group was not statistically significant (P 0.05).【Conclusion】 The PARP inhibitor 3 -AB 20 mg/kg administered intravenously was safe,effective and optimal dosage for attenuating the severity of severe acute pancreatitis