Inhibition of nuclear factor-κB activation improves the survival of rats with taurocholate pancreatitis
Inhibition of nuclear factor-κB activation improves the survival of rats with taurocholate pancreatitis
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DOI：
10.1136/gut.44.2.253
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发表时间：
1999-02-01
期刊：
影响因子：
24.5
通讯作者：
Toyota, T
中科院分区：
文献类型：
--
作者：
Satoh, A;Shimosegawa, T;Toyota, T
背景：重症急性胰腺炎早期死亡常为多器官功能障碍，但其机制尚不明确。目的：探讨致死性胰腺炎大鼠巨噬细胞中核因子κB（NF-κB）的状态，并评价NF-κB抑制剂吡咯烷二硫代氨基甲酸酯对病理和死亡率的影响。比较接受吡咯烷二硫代氨基甲酸酯 (PDTC) 治疗和未接受治疗的大鼠的疾病严重程度、死亡率以及腹膜和肺泡巨噬细胞中 NF-κB 的激活。结果-牛磺胆酸盐胰腺炎导致胰腺大片坏死、出血和严重白细胞浸润，以及肺肺泡间隔增厚。胰腺炎诱导后六小时，腹膜和肺泡巨噬细胞中的 NF-κ B 被激活。 PDTC预处理剂量依赖性地减弱了NF-κB的激活并提高了大鼠的存活率，尽管它不影响血清淀粉酶的早期升高和组织学结果。结论-早期阻断NF-κB的激活可能有效减少重症急性胰腺炎的致命结果。
Background-Death in the early stages of severe acute pancreatitis is frequently the result of multiple organ dysfunction, but its mechanism is not clear.Aims-To investigate the state of nuclear factor-kappa B (NF-kappa B) in macrophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-kappa B, on the pathology and mortality.Methods-Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-kappa B in peritoneal and alveolar macrophages were compared in rats receiving pyrrolidine dithiocarbamate (PDTC) treatment and those that were not.Results-Taurocholate pancreatitis produced massive necrosis, haemorrhage, and severe leucocyte infiltration in the pancreas as well as alveolar septal thickening in the lung. NF-kappa B was activated in peritoneal and alveolar macrophages six hours after pancreatitis induction. Pretreatment with PDTC dose-dependently attenuated the NF-kappa B activation and improved the survival of the rats, although it did not affect the early increase in serum amylase and histological findings.Conclusions-Early blockage of NF-kappa B activation may be effective in reducing fatal outcome in severe acute pancreatitis.