The Effects of Activated Protein C on Experimental Severe Acute Pancreatitis
|Keywords||Severe Acute Pancreatitis SAP Protein C PC Rats Experimental Whole blood apparent viscosity Tumor necrosis factor-α INF-α Interleukin-6 IL-6 Recombinant human activated protein C rhAPC Treatment Prognosis TNF-α IL-6 MPO Pathology score Acute lung injury ALI Systemic inflammatory response syndrome SIRS|
Objective: To investigate the role of protein C in severe acute pancreatitis.Methods: 50 male Sprague-dawley rats were randomized into 2 groups, experimental (severe acute pancreatitis group, n=45) or control group (n=5). Sham operation was conducted in the control group, while 5% sodium taurocholate retrobiliopancreatic duct injection was conducted in the experimental group to induce severe acute pancreatitis. Samples of pancreas tissue and blood were harvested 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours or 14 hours after operation. Plasm protein C, plasm AMS, plasm tumor necrosis factor alfa, plasm interleukin-6, ascites volume and blood apparent viscosity was measured.Results: Pancreas edema, necrosis and hemorrage were observed in experimental group. Ascites increased quickly in the early 4 hours. TNF-α, IL-6' dissertation">IL-6, ascites volume and blood apparent viscosity increased significantly in experimental group compared to control group. Protein C level decreased 1 hour after operation, almost to be 30% 4 hours after operation and kept at a very low level in the follow period. Protein C level was in negative correlation to TNF-α, IL-6, ascites volume and blood apparent viscosity.Conclusion: Protein C decreased significantly in the early stage of severe acute pancreatitis. It suggested that protein C play an important role in the pathogenisis and progression of severe acute pancreatitis. OBJECTIVE: To evaluate the therapeutic effects of recombinant human activated protein C in an animal model of severe acute pancreatitis.METHODS:DESIGN: Laboratory investigation, case control study.SUBJECTS: Male Sprague-Dawley rats weighing 150-190 g.INTERVENTIONS: All animals anesthetized by 1% pentobarbital were subjected to ST injection to induce severe acute pancreatitis and were randomly divided into two groups. A bolus injection of normal saline (5ml/kg body weight ) or recombinant human activated protein C (drotrecogin alfa, activated) was conducted via caudal vein 10 min after the onset of SAP (50μg/kg body weight, 10μg/ml). Pancreas, lung and blood samples were done 2 hours, 6hours and 12 hours after the onset of SAP. Plasm AMS, plasm TNF-α, plasm IL-6, blood apparent viscosity were measured. Tissue injury was assessed by pathologic score of pancreas or lung. Myeloperoxidase concentration was detected in pancreas and lung.RESULTS: Those SAP reactions were all significantly suppressed by resuscitation with activated protein C. Plasm TNF-α, plasm IL-6, myeloperoxidase in pancreas and lung, blood apparent viscosity decreased significantly in the treated group compare to those in the SAP group. But plasm AMS and the pathologic score of pancreas were not improved significantly in present study. CONCLUSIONS: The present study suggests that APC has potent anticoagulatant and anti-inflammatory actions in experimental severe acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.