BACKGROUND: Acute lung injury (ALI) is a common and serious complication of severe acute pancreatitis (SAP). The study aimed to investigate the protective effect and mechanism of phosphatidylinositol-3 kinase (PI3K) inhibitor Wortmannin in SAP associated with ALI. METHODS: Ninety rats were randomly divided into three groups: sham operation (SO) group (n=30), SAP group (n=30), and SAP+Wortmannin (SAP+W) group (n=30). SAP model was induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct of rats. The rate of lung water content, myeloperoxidase (MPO), matrix metalloproteinase 9 (MMP-9), protein kinase B (PKB), abdphosphorylation of protein kinase B (P-PKB) activity in the lung tissue were evaluated. RESULTS: In the SAP group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours (P<0.05); the rate of lung water content, MPO and TNF-α activity were also gradually increased, and the degree of lung lesion gradually increased (P<0.05). In the SAP+Wortmannin group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours; it was higher than that in the SO group (P<0.05), but significantly lower than that in the SAP group (P<0.05). The rest indicators in the SAP+Wortmannin group were also significantly decreased as compared with the SAP group (P<0.05). CONCLUSIONS: The expression of phosphatidylinositol-3 kinase/protein kinase B was elevated in severe pancreatitis rats with lung injury. This suggested that PI3K signal transduction pathway is involved in the control and release of proinflammatory cytokines TNF-α, which may play an important role in the pathogenesis of severe acute pancreatitis associated with lung injury. This finding indicated that Wortmannin can block the PI3K signal transduction pathway, and inhibit the release of inflammatory factor TNF-α.
BACKGROUND:Acute lung injury (ALI) is a common and serious complication of severe acute pancreatitis (SAP). The study aimed to investigate the protective effect and mechanism of phosphatidylinositol-3 kinase (PI3K) inhibitor Wortmannin in SAP associated with ALI. METHODS: Ninety rats were randomly divided into three groups: sham operation (SO) group (n=30), SAP group (n=30), and SAP+Wortmannin (SAP+W) group (n=30). SAP model was induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct of rats. The rate of lung water content, myeloperoxidase (MPO), matrix metalloproteinase 9 (MMP-9), protein kinase B (PKB), abdphosphorylation of protein kinase B (P-PKB) activity in the lung tissue were evaluated. RESULTS: In the SAP group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours (P<0.05); the rate of lung water content, MPO and TNF-α activity were also gradually increased, and the degree of lung lesion gradually increased (P<0.05). In the SAP+Wortmannin group, the p-PKB expression in the lung tissue began to rise at 3 hours after modeling, and peaked at 12 hours; it was higher than that in the SO group (P<0.05), but significantly lower than that in the SAP group (P<0.05). The rest indicators in the SAP+Wortmannin group were also significantly decreased as compared with the SAP group (P<0.05). CONCLUSIONS: The expression of phosphatidylinositol-3 kinase/protein kinase B was elevated in severe pancreatitisrats with lung injury. This suggested that PI3K signal transduction pathway is involved in the control and release of proinflammatory cytokines TNF-α, which may play an important role in the pathogenesis of severe acute pancreatitis associated with lung injury. This finding indicated that Wortmannin can block the PI3K signal transduction pathway, and inhibit the release of inflammatory factor TNF-α.
Authors: V P Singh; A K Saluja; L Bhagat; G J van Acker; A M Song; S P Soltoff; L C Cantley; M L Steer Journal: J Clin Invest Date: 2001-11 Impact factor: 14.808
Authors: Tobias Keck; James H Balcom; Carlos Fernández-del Castillo; Bozena A Antoniu; Andrew L Warshaw Journal: Gastroenterology Date: 2002-01 Impact factor: 22.682
Authors: Jason A Gustin; Osman N Ozes; Hakan Akca; Roxana Pincheira; Lindsey D Mayo; Qiutang Li; Javier Rivera Guzman; Chandrashekhar K Korgaonkar; David B Donner Journal: J Biol Chem Date: 2003-10-29 Impact factor: 5.157