Protection effect of triptolide to liver injury in rats with severe acute pancreatitis.
BACKGROUND
The high mortality of patients with severe acute pancreatitis (SAP) is due to multiorgan dysfunction. The mechanisms of SAP are still obscure. The aim of this study was to investigate the role of nuclear factor-kappa B (NF-kappaB) activation in rats with SAP associated with liver injury and the protection effect of triptolide against liver injury in rats with SAP.


METHODS
Ninety Wistar rats were randomly divided into three groups (n=30 each group): severe acute pancreatitis (group P), treatment with triptolide (group T), and sham operation (group S). SAP models were induced by retrograde injection of 5% sodium taurocholate to the pancreatic duct. After the model was successfully established, no treatment was given to group P. In group T, triptolide (0.05 mg/ml) was injected intraperitoneally (0.2 mg/kg). In group S, the abdominal walls of rats were opened, sutured, but not treated. The rats were sacrificed after operation at 2, 6, and 12 hours, respectively. The serum levels of amylase (AMY), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined at three time points (10 rats for each time point). Liver tissues were obtained to detect the activity of NF-kappaB and to observe their pathological changes with light and electron microscopes.


RESULTS
The serum levels of AMY and ALT were higher in groups P and T than in group S. The serum AMY levels were significantly lower in group T than in group P at 12 hours after operation. The serum ALT levels were significantly lower in group T than in group P at 6, 12 hours after operation. At the three time points, the levels of TNF-alpha and IL-6 in groups P and T increased more significantly than in group S. In group T they were decreased more significantly than in group P at the three time points. In groups P and T, NF-kappaB activity in liver tissue increased more significantly than in group S at the three time points. The activity of NF-kappaB was higher in group P than in groups S and T at the three time points. Liver pathological damages were milder in group T than in group P under light and electron microscopes.


CONCLUSIONS
NF-kappaB plays an important role in the pathogenesis of liver injury in rats with SAP. Triptolide can reduce pathological damage to the liver. Its mechanism is to inhibit the activity of NF-kappaB and to decrease the release of inflammatory mediators.
Zhao
Yong-Fu
YF
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhai
Wen-Long
WL
Zhang
Shui-Jun
SJ
Chen
Xiao-Ping
XP
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds; D005260:Female; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008107:Liver Diseases / Q000188:drug therapy / Q000209:etiology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy*; D010616:Phenanthrenes / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D015850:Interleukin-6; D016328:NF-kappa B; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; C001899:triptolide