Zhao Yong-Fu, Zhai Wen-Long, Zhang Shui-Jun, Chen Xiao-Ping
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hepatobiliary Pancreat Dis Int. 2005 Nov;4(4):604-8.
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.
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.
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.
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.
重症急性胰腺炎（SAP）患者的高死亡率归因于多器官功能障碍。SAP的发病机制仍不清楚。本研究旨在探讨核因子-κB（NF-κB）激活在伴有肝损伤的SAP大鼠中的作用以及雷公藤甲素对SAP大鼠肝损伤的保护作用。
90只Wistar大鼠随机分为三组（每组n = 30）：重症急性胰腺炎组（P组）、雷公藤甲素治疗组（T组）和假手术组（S组）。通过向胰管逆行注射5%牛磺胆酸钠诱导建立SAP模型。模型成功建立后，P组不给予任何处理。T组腹腔注射雷公藤甲素（0.05 mg/ml，0.2 mg/kg）。S组打开大鼠腹壁，缝合，但不进行处理。分别在术后2、6和12小时处死大鼠。在三个时间点测定血清淀粉酶（AMY）、丙氨酸氨基转移酶（ALT）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平（每个时间点10只大鼠）。取肝脏组织检测NF-κB活性，并通过光镜和电镜观察其病理变化。
P组和T组血清AMY和ALT水平高于S组。术后12小时T组血清AMY水平显著低于P组。术后6、12小时T组血清ALT水平显著低于P组。在三个时间点，P组和T组TNF-α和IL-6水平升高比S组更显著。在三个时间点T组下降比P组更显著。在三个时间点，P组和T组肝组织中NF-κB活性升高比S组更显著。在三个时间点P组NF-κB活性高于S组和T组。光镜和电镜下T组肝脏病理损伤比P组轻。
NF-κB在SAP大鼠肝损伤发病机制中起重要作用。雷公藤甲素可减轻肝脏病理损伤。其机制是抑制NF-κB活性并减少炎症介质释放。
