Antioxidant Inhibits HMGB1 Expression and Reduces Pancreas Injury in Rats with Severe Acute Pancreatitis

作者：Zhang Zhong Wei^*; Zhang Qi Yu; Zhou Meng Tao; Liu Na Xin; Chen Tong Ke; Zhu Ye Fan; Wu Liang

来源：Digestive Diseases and Sciences, 2010, 55(9): 2529-2536.

DOI：10.1007/s10620-009-1073-0

• Severe acute pancreatitis
• NF-kappa B
• High-mobility group box protein-1
• Pyrrolidine dithiocarbamate

Pathogenesis of severe acute pancreatitis is still unclear, which leads to a lack of proper treatment in severe acute pancreatitis therapeutic strategy.
To investigate the effect of treatment with antioxidant pyrrolidine dithiocarbamate on pancreas injury in rats with severe acute pancreatitis and its possible mechanism.
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-kappa B activation, tumor necrosis factor-alpha levels and high-mobility group box protein-1 expression levels in pancreatic tissue were studied.
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-kappa B activity, tumor necrosis factor-alpha, high-mobility group box protein-1 levels in the pyrrolidine dithiocarbamate-treated group all remarkably decreased (p < 0.05).
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-kappa B 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.

• 出版日期2010-9
• 单位温州医科大学