Abstract
Objective To observe the protective and therapeutic effect of wortmannin, inhibitor of phosphatidylinositol 3-kinase (PI3K), on severe acute pancreatitis (SAP) in rats and investigate its mechanism. Methods Ninety SD rats were randomly divided into 5 groups:control group, control+wortmannin group, SAP group, before SAP+ wortmannin group and after SAP+ wortmannin group (n=18 per group). SAP model was induced by retrograde infusion of 50 g/L sodium taurocholate into the biliopancreatic duct of rats. Serum level of tumor necrosis factor-alpha (TNF-α), serum level of amylase,myeloperoxidase (MPO) activity of pancreatic tissue and the protein content of bronchoalveo-lar lavage fluids (BALF) were evaluated. Histopathological changes of lung and pancreas were ob-served. Results In SAP group, serum level of TNF-α, serum level of amylase, MPO activity of pan-creatic tissues and the protein content of BALF were significantly elevated (P<0.01). The lung and pancreas injuries were gradually aggravated with disease progression. All the indicators of before SAP + wortmannin group and after SAP+ wortmannin group were also elevated as compared with the con-trol group, but still significantly decreased as compared with SAP group (P<0.01). There was no statistical difference between the two groups. All indicators of control+ wortmannin group and control group had no statistical difference either. Conclusion Pretreatment and treatment with wortmannin could decrease the severity of pancreatitis in rats. The mechanism may be the inhibition on the activity of PI3K in pancreatic acinar cell, thus calcium overload is decreased and the activation of trypsinogen is inhibited to certain extent. Furthermore, there is the inhibition on activation of PI3K in polymorpho-nuclear neutrophils (PMN), further on the activation of many kinds of inflammatory cells and on the release of TNF-a and other inflammatory factors. Key words: Pancreatitis; Wortmannin; Neutrophil; PI3K; Calcium overload; Trypsinogen; Injury/lung
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