Therapeutic effect of wortmannin on acute pancreatitis with renal dysfunction and on phosphatidylinositol 3 kinase/protein kinase B signaling pathway

Abstract

Objective To explore the therapeutic effect of wortmannin on acute pancreatitis(AP) with renal dysfunction and on phosphatidylinositol 3 kinase(PI3K)/protein kinase B(PKB)signaling pathway. Methods Eighty healthy male SD rats were randomly divided into normal control group, sham operation group(SO group), AP group and wortmannin group.SO group, AP group and wortmannin group were further divided into 3, 6 and 12 h sub-groups(n= 8 each).The AP model was established by bile duct retrograde injection.Wortmannin was intraperitoneally injected 4 h before operation.Serum urea nitrogen, creatinine, amylase, pathological findings of the kidney and pancreas, and PKB, p-PKB and tumor necrosis factor-α(TNF-α) proteins in the kidney and pancreas were observed. Results Histopathological damage of the kidney and pancreas was severer, blood urea nitrogen[(9. 81±1. 28) and(77. 49± 1. 17)vs.(5. 33±0. 32)mmol/L], creatinine[(62. 19±5. 84)and(55. 12±5. 27) vs.(45. 13±3. 01) μmol/L]and amylase levels[(2 931±619) and(2 061±897) vs.(677±120) U/L] were significantly higher in AP group and wortmannin group than in SO group 3 h after operation(P<0. 05), more significantly in 6 h and 12 h sub-groups. Histopathological damage of the kidney and pancreas was severed, blood urea nitrogen[(16. 51±2. 00) vs.(21. 16±2. 57) mmol/L], creatinine[(94. 63±11. 30) vs. (116. 24±14. 82)μmol/L], amylase levels[(3 264±932)vs.(7 725±1 517) U/L], p-PKB(1. 01± 0. 24 vs.1. 23±0. 30)and TNF-αproteins(1. 11±0. 29 vs.1. 33±0. 37)levels were significantly lower in wortmannin group than in AP group at 12 h after operation(P<0. 05). Conclusion Activation of PI3K/ PKB signaling pathway plays a very important role in the occurrence and development of AP with renal function dysfunction.PI3K inhibitors(wortmannin)can significantly alleviate the renal function damage induced by AP. Key words: Acute pancreatitis; Renal injury; Phosphatidylinositol 3 kinase/protein kinase B signaling pathway; Phosphatidylinositol 3 kinase inhibitor