Effects of CC-4047 in a Mouse Model of Cerulein-induced Acute Pancreatitis
| Autor: | Ming-jen Tsai, 蔡銘仁 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 Acute pancreatitis is characterized by intraacinar enzyme activation and subsequent dysregulation in immune response. Overproduction of proinflammatory mediators in response to severe pancreatitis contributes to the systemic inflammatory response, whose entity may, in the end, develop into multi-organ damage and even mortality. Recently, it has been shown that TNF-α and other inflammatory cytokines, IL-1β, IL-6 and MCP-1, may be novel targets for the treatment of acute pancreatitis. CC-4047, an immunomodulatory agent and analog of thalidomide, exhibits 20,000-fold greater inhibitory effect on TNF-α release and less neurologic side effects than thalidomide. The aim of this study was to assess the therapeutic effects of CC-4047 in a murine model of acute pancreatitis. Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein (100 μg/kg/hr X 8); in another group of animals, CC-4047 was administered (0.5 mg/kg orally) 1 hour before the first cerulein injection (pre-treatment group) or after the last cerulein injection (post-treatment group). Mice were sacrificed at different time points after the induction of pancreatitis to examine the plasma amylase and lipase activities, histological features, and inflammatory mediators of pancreas. Our results showed that the plasma level of amylase and lipase, histological injury of pancreatitis, MCP-1 and iNOS expression in pancreas were significantly reduced when pre-treated with CC-4047 in mice with acute pancreatitis. Post-treatment with CC-4047 also showed inhibitory effect on cerulein-induced elevation of amylase and lipase. Therefore, CC-4047 treatment prevents and attenuates the development of cerulein-induced acute pancreatitis in mice. Our data suggest that CC-4047 may become a new therapeutic candidate in the future clinical treatment of acute pancreatitis. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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