BACKGROUND AND AIMS: Activated protein C (APC) is increasingly understood to have diverse regulatory functions in inflammation. However, the exact mechanism of action remains unclear in severe acute pancreatitis (SAP). The aim of this study was to demonstrate the effects of APC on expressions of thrombomodulin (TM) and endothelial cell protein C receptor (EPCR), and its subsequent effect on the severity of SAP. METHODS: Sprague-Dawley rats were randomly divided into four groups. The rats were given intravenous injections of APC (50, 10 microg/kg, respectively, treated groups) or saline (SAP group) just before induction of SAP. One group of rats underwent only sham operation as control group. Experimental samples were harvested at 16 h after induction. The protein and mRNA levels of matrix metalloprotease 9 (MMP-9), TM, and EPCR in pancreatic tissue were investigated. Serum tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) levels were determined. The severity of disease was evaluated by histological score of pancreatic injury, wet/dry weight ratio of pancreatic tissue, and serum amylase. RESULTS: In the APC 50 microg/kg-treated group, serum TNF-alpha, IL-8, and pancreatic MMP-9 levels were decreased and the levels of pancreatic EPCR and TM were up-regulated compared with the SAP group. A significant dose-dependent relationship was found between the decreased levels of serum IL-8 and the APC-treated dosage. Furthermore, the severity of SAP was ameliorated by APC treatment. CONCLUSIONS: APC could augment the anti-coagulation and anti-inflammatory activity by up-regulating EPCR and TM expressions, thus attenuating the severity of SAP.
BACKGROUND AND AIMS: Activated protein C (APC) is increasingly understood to have diverse regulatory functions in inflammation. However, the exact mechanism of action remains unclear in severe acute pancreatitis (SAP). The aim of this study was to demonstrate the effects of APC on expressions of thrombomodulin (TM) and endothelial cell protein C receptor (EPCR), and its subsequent effect on the severity of SAP. METHODS:Sprague-Dawley rats were randomly divided into four groups. The rats were given intravenous injections of APC (50, 10 microg/kg, respectively, treated groups) or saline (SAP group) just before induction of SAP. One group of rats underwent only sham operation as control group. Experimental samples were harvested at 16 h after induction. The protein and mRNA levels of matrix metalloprotease 9 (MMP-9), TM, and EPCR in pancreatic tissue were investigated. Serum tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) levels were determined. The severity of disease was evaluated by histological score of pancreatic injury, wet/dry weight ratio of pancreatic tissue, and serum amylase. RESULTS: In the APC 50 microg/kg-treated group, serum TNF-alpha, IL-8, and pancreaticMMP-9 levels were decreased and the levels of pancreaticEPCR and TM were up-regulated compared with the SAP group. A significant dose-dependent relationship was found between the decreased levels of serum IL-8 and the APC-treated dosage. Furthermore, the severity of SAP was ameliorated by APC treatment. CONCLUSIONS: APC could augment the anti-coagulation and anti-inflammatory activity by up-regulating EPCR and TM expressions, thus attenuating the severity of SAP.
Authors: Guido Alsfasser; Andrew L Warshaw; Sarah P Thayer; Bozena Antoniu; Michael Laposata; Kent B Lewandrowski; Carlos Fernández-del Castillo Journal: Arch Surg Date: 2006-07
Authors: Outi Lindstrom; Leena Kylanpaa; Panu Mentula; Pauli Puolakkainen; Esko Kemppainen; Reijo Haapiainen; Jose A Fernandez; John H Griffin; Heikki Repo; Jari Petaja Journal: Crit Care Date: 2006-02 Impact factor: 9.097
Authors: Ville Pettilä; Lea Kyhälä; Marja-Leena Kylänpää; Ari Leppäniemi; Minna Tallgren; Antti Markkola; Pauli Puolakkainen; Heikki Repo; Esko Kemppainen Journal: Crit Care Date: 2010-07-27 Impact factor: 9.097