Abstract:
Objective To investigate the effects and mechanisms of poly adenosine diphosphate (ADP) ribose polymerase inhibitor 3aminobenzamide (3AB) on kidney injury in rates with severe acute pancreatitis (SAP).
Methods Fiftysix male Wistar rats were divided into the sham operation (SO) group, SAP (3, 6, 12 hours) groups, and 3AB+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 3AB+SAP group were infused with 3AB (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 ADPribose formation, intercellular adhesion molecules1 (ICAM1) and Pselectin 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 KruskalWallis 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 3AB+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 3AB+SAP groups. There were significant differences in the levels of blood urea nitrogen between the SAP group and the 3AB+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 3AB+SAP groups. There were significant differences in the levels of creatinine between the SAP group and the 3AB+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 3AB+SAP groups. There were significant differences in the renal MPO activity between the SAP group and the 3AB+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 3AB+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 3AB+SAP 12 hours group were significantly slighter (P<0.05). The relative expressions of poly ADPribose, ICAM1 and Pselectin 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 polyADPribose, ICAM1 and Pselectin of the 3AB+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 ADPribose polymerase inhibitor 3AB protects kidney from injury in the experimental SAP rats. Poly ADPribose polymerase inhibitor 3AB functions by suppressing the ICAM1 and Pselectin expression and reducing neutrophil infiltration.