Effect of phosphatidylinositol-3 kinase inhibitor Wortmannin on pathogenesis of severe acute pancreatitis associated with acute lung injury

Abstract

Objective To investigate the protective effect and mechanism of phosphatidylinositol-3 kinase (PI3K) inhibitor Wortmannin in severe acute pancreatitis (SAP) associated with acute lung injury.Methods Fifty-six rats were randomly divided into 3 groups:sham operation (SO) group ( n =8 ),SAP group (n =24),and SAP + Wortmannin (SAP + W) group (n =24).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 ),abd phosphorylation of protein kinase B (p-PKB) activity in the lung tissue were evaluated.Results In SAP group,the p-PKB expression in the lung tissue began to rise at 3 h after modeling,and reached the peak at 12 h (582.95 ±34.72 vs 191.34 ±39.53) (P ＜0.05) ; the rate of lung water content,MPO,and MMP9 activity were also gradually increased,and the degree of lung lesion gradually increased ( P ＜ 0.05 ) ; in SAP + Wortmannin group,the p-PKB expression in the lung tissue began to rise at 3 h after modeling,reached the peak at 12 h,and higher than in SO group (455.65 ± 40.47 vs 191.34 ± 39.53) (P ＜0.05),but significantly lower than that in SAP group (455.65 ±40.47 vs 582.95 ±34.72) (P ＜0.05).The rest indicators in SAP + Wortmannin group were also significantly decreased as compared with SAP group ( P ＜ 0.05 ).Conclusion Pretreatment with wortmannin could decrease the lung lesion of rats with SAP probably by inhibiting the activation of phosphatidylinositol 3-kinase signal transduction pathway in polymorphonuclear neutrophils (PMN),reducing PMN activation and migration,further more,suppressing the release of MMP-9 and other inflammatory factors. Key words: Wortmannin; Phosphatidylinositol-3 kinase/protein kinase B; Severe acute pancreatitis; Acute lung injury