Antioxidant inhibits HMGB1 expression and reduces pancreas injury in rats with severe acute pancreatitis.
Dig Dis Sci
; 55(9): 2529-36, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-19997973
ABSTRACT
BACKGROUND:
Pathogenesis of severe acute pancreatitis is still unclear, which leads to a lack of proper treatment in severe acute pancreatitis therapeutic strategy.OBJECTIVE:
To investigate the effect of treatment with antioxidant pyrrolidine dithiocarbamate on pancreas injury in rats with severe acute pancreatitis and its possible mechanism.METHODS:
A total of 144 male Sprague-Dawley rats were randomly allocated into a sham operation group (n=48), a severe acute pancreatitis group (n=48), and a pyrrolidine dithiocarbamate-treated group (n=48). All the rats were killed at 1, 3, 6, 12, 24, and 48 h after operation. The pancreas histopathologies were observed and serum amylase levels were tested. Meanwhile, the nuclear factor-kappaB activation, tumor necrosis factor-alpha levels and high-mobility group box protein-1 expression levels in pancreatic tissue were studied.RESULTS:
Animals receiving pyrrolidine dithiocarbamate had significantly improved pancreas histopathology and lower serum amylase levels (p<0.05). In the severe acute pancreatitis group, pancreas tumor necrosis factor-alpha levels reached a peak at 6 h after operation and afterwards rapidly declined to normal levels. However, high-mobility group box protein-1 levels in pancreatic tissue increased remarkably at the 12th hour, reached a peak at 24 h, and maintained up to 48 h post-severe acute pancreatitis. Compared to the severe acute pancreatitis group, the pancreas nuclear factor-kappaB activity, tumor necrosis factor-alpha, high-mobility group box protein-1 levels in the pyrrolidine dithiocarbamate-treated group all remarkably decreased (p<0.05).CONCLUSIONS:
High-mobility group box protein-1 seems to act as a late cytokine mediator in the pathogenesis of severe acute pancreatitis. Pyrrolidine dithiocarbamate might inhibit the activation of nuclear factor-kappaB to blockade tumor necrosis factor-alpha, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
/
Pancreatite
/
Pirrolidinas
/
Tiocarbamatos
/
Proteína HMGB1
/
Antioxidantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article