Effect of poly adenosine diphasphate-ribose polymerase inhibitor on renal injury in rats with severe acute pancreatitis

Abstract

Objective To investigate the effects and mechanisms of poly adenosine diphosphate (ADP)-ribose polymerase inhibitor 3-aminobenzamide (3-AB) on kidney injury in rates with severe acute pancreatitis (SAP).Methods Fifty-six male Wistar rats were divided into the sham operation (SO) group,SAP (3,6,12 hours) groups,and 3-AB + SAP (3,6,12 hours) groups,and there were 8 rats in each group.SAP model was established by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.Rats in the 3-AB + SAP group were infused with 3-AB (20 μg/g) via femoral vein 30 minutes before SAP model establishment.The serum amylase,kidney function and renal myeloperoxidase (MPO) were determined,and pathological scores of pancreatic and renal tissues were evaluated under light microscope.Renal poly ADP-ribose formation,intercellular adhesion molecules-1 (ICAM-1) and P-selectin expression were detected by the Western blot.All data were analyzed using the analysis of variance or t test.Renal injury grading was analyzed using the Kruskal-Wallis nonparametric test.Results The levels of serum amylase of SAP 3,6,12 groups were (3806 ± 229)U/L,(4898 ± 295) U/L and (5726 ± 372) U/L,which were significantly higher than (2785 ± 160) U/L,(3241 ± 198) U/L and (3953 ± 249) U/L of the 3-AB + SAP groups (t =3.652,4.672,4.407,P ＜ 0.05).The levels of blood urea nitrogen were (11.6 ± 0.8) mmol/L,(19.3 ± 1.3) mmol/L and (29.6 ± 2.1) mmol/L,which were higher than (7.5 ± 0.5) mmol/L,(10.5 ± 0.7) mmol/L and (21.6 ± 1.5) mmol/L of the 3-AB + SAP groups.There were significant differences in the levels of blood urea nitrogen between the SAP group and the 3-AB + SAP group at the 6 and 12 hours (t =3.836,6.849,P ＜0.05).The levels of creatinine of the SAP 3,6,12 hours groups were (48.7 ±3.1) μmol/L,(58.3 ±3.7) μmol/L and (75.9 ±5.4) μmol/L,which were higher than (40.7 ±2.6)μmol/L,(43.2 ± 2.6) μmol/L and (53.4 ± 3.2) μmol/L of the 3-AB + SAP groups.There were significant differences in the levels of creatinine between the SAP group and the 3-AB + SAP group at the 6 and 12 hours (t =3.279,3.073,P ＜ 0.05).The renal MPO activity of the SAP 3,6,12 hours groups were (0.69 ± 0.06) U/g,(1.07 ± 0.09)U/g and (1.42 ±0.13)U/g,which were higher than (0.57 ±0.05)U/g,(0.75 ±0.06)U/g and (0.89 ± 0.07) U/g of the 3-AB + SAP groups.There were significant differences in the renal MPO activity between the SAP group and the 3-AB + SAP group at the 6 and 12 hours (t =3.066,4.012,P ＜ 0.05).The pancreatic pathological scores of the SAP 3,6 and 12 hours group were 6.50 ± 0.53,9.06 ± 0.66 and 11.75 ± 0.89,which were significantly higher than 4.25 ± 0.31,6.06 ± 0.51 and 7.57 ± 0.59 of the 3-AB + SAP group (t =3.631,3.598,5.147,P ＜ 0.05).The structure of the kidney was normal in the SO group.Congestive changes were observed in glomerulus of kidney,the renal tubular epithelial cell was necrosed,and luminal narrowing or occlusion,hemorrhage in the intercellular substance and inflammatory cell infiltration were observed in the SAP 12 hours group.The pathological changes of the 3-AB + SAP 12 hours group were significantly slighter (P ＜ 0.05).The relative expressions of poly ADP-ribose,ICAM-1 and P-selectin of the SO group were 1.00 ±0.21,1.00 ±0.18,1.00 ± 0.16,which were significantly lower than 3.83 ± 0.63,5.42 ± 0.83,3.71 ± 0.48 of the SAP 12 hours group (t =6.955,23.107,10.352,P ＜ 0.05).The relative expressions of poly-ADP-ribose,ICAM-1 and P-selectin of the 3-AB + SAP 12 hours group were 1.94 ± 0.36,2.35 ± 0.35,2.11 ± 0.29,which were significantly lower than SAP 12 hours group (t =3.977,12.115,5.012,P ＜ 0.05).Conclusions Poly ADP-ribose polymerase inhibitor 3-AB protects kidney from injury in the experimental SAP rats.Poly ADP-ribose polymerase inhibitor 3-AB functions by suppressing the ICAM-1 and P-selectin expression and reducing neutrophil infiltration. Key words: Pancreatitis, severe acute; Renal injury; Poly adenosine diphasphate-ribose polymerase; 3-aminobenzamide; Myeloperoxidase