The Protective Effects of Protease Inhibitors of Aprotinin and Matrix Metalloproteinases Inhibitor on the Lung Injury Induced by Sodium Glycodeoxycholate-Associated Pancreatitis

• Main Authors: Tsai Shih-Wen, 蔡詩文
• Other Authors: Wang David
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/38796528800810776630

碩士 === 輔仁大學 === 基礎醫學研究所碩士班 === 96 === Acute lung injury is the extrapancreatic complication most frequently associated with the high rates of morbidity and mortality in severe acute pancreatitis but the mechanisms involved are not clear. Translocation of pancreatic juice from the pancreas into the systemic circulation might be the causes to induce lung injury and multiple organ injury. In this study we induced acute pancreatitis by intrapancreatic duct infusion of 10 mM sodium glycodeoxycholate (GDOC) (0.4 ml/kg in saline) within 10 minutes and then ligated the pancreatic duct. 48 hours later we observed the injuries in organs of the lung and the pancreas. We analyzed the inflammatory responses by measuring the changes in blood concentration of WBC, H2O2, NO, and IL6. Pancreatic injury was analyzed by measuring changes in blood concentrations of amylase, LDH and the wet/dry weight ratio of the pancreas. Lung injury was analyzed by measuring changes in wet/dry lung weight ratio and lavage protein concentration. Pharmacological interventions, including pretreatments of protease inhibitors of aprotinin (10mg/kg) and Matrix metalloproteinases inhibitor (MMPi, 100μg/kg), were applied in this pancreatitis model. After experiments, pancreatic tissue and lung tissue were collected for analyzing of mRNA and protein expressions of iNOS, MMP-2 and MMP-9 by real time PCR and Western blot. Histological changes in pancreatic and lung tissues (H&E stain) and PMN sequestered in the lung tissues were analyzed. The results show that intrapancreatic duct administration of GDOC could induce necrotic and edematic pancreatitis and lung injury. Blood concentration of pancreatic enzymes increased and the systemic inflammatory responses ensuring (increases in blood concentrations of WBC, H2O2, NO, and IL6). mRNA and protein expressions of inflammatory mediators such as iNOS and MMP were significantly increased in both pancreatic tissues and lung tissues. Protease inhibitors of aprotinin and MMPi significantly attenuated pancreatitis, lung injury and systemic inflammatory responses. We demonstrate that pancreatitis-induced activation of proteases such as serine protease and MMP are involved in the GDOC-induced acute pancreatitis, systemic inflammatory responses and lung injury.