Mediators for the aggravation of acute pancreatitis-the role of cytokies and activated neutrophils

本研究旨在探讨细胞因子和活化中性粒细胞在大鼠视神经蛋白诱导的急性胰腺炎加重中的作用。这些介质可诱发多器官衰竭。在体外实验中，cerulein诱导的胰腺炎大鼠腹腔巨噬细胞对脂多糖（LPS）产生的肿瘤坏死因子- α (tnf - α)的反应明显增强。非胰腺炎大鼠腹腔注射LPS作为脓毒性刺激。(1) LPS组胰腺炎大鼠血清tnf - α水平明显高于非胰腺炎大鼠。(2)与非胰腺炎大鼠相比，LPS对胰腺炎大鼠支气管肺泡巨噬细胞体外产生tnf - α的影响显著增强。(3)与非胰腺炎组相比，LPS组胰腺炎大鼠肺中性粒细胞蓄积增加。(4)此外，LPS可显著提高胰腺炎大鼠肺髓过氧化物酶活性。(5)原位硝基蓝特拉唑（NBT）法测定的胰腺巨噬细胞的超氧化物生成也增强了LPS的作用。(6)肝功能障碍主要出现在LPS大鼠中。LPS诱导的胰腺炎大鼠24小时存活率明显短于非胰腺炎大鼠。蛋白酶抑制剂的施用倾向于减少细胞因子的产生和肝功能障碍的胰腺炎大鼠与LPS。因此，当涉及内毒素血症时，胰腺炎大鼠会遇到高细胞分裂血症和远端器官衰竭。在cerulein诱导的急性胰腺炎中，第二次给药LPS可诱导并激活巨噬细胞释放大量细胞因子。结果，中性粒细胞积聚到远端器官，导致组织破坏。施用蛋白酶抑制剂有改善这些器官衰竭的趋势。然而，还需要进一步的实验。少

The present sudy was undertaken to investigate the roles of cytokines and activated neutrophils on the aggravation of cerulein-induced acute pancreatitis in rats. These mediators may induce multiple organ failures.1.In vitro tumot necrosis factor-alpha (TNF-alpha) production in response to lipopolysaccharide (LPS) by peritoneal macrophages taken from cerulein-induced pancretitis rats was signifcantly enhanced compared to that odserved in naive controls.2.Pancreatitis of non-pancreatitis rats were injected intraperitoneally with LPS as a septic challenge.(1) Serum levels of TNF-alpha in pancreatitis rats with LPS were significantly higher than those in non-pancreatitis rats with LPS.(2) In vitro TNF-alpha production by bronchoalveolar macrophages obtained from pancreatitis rats with LPS were significantly enhaced compared to those in non-pancreatitis rats with LPS.(3) Neutrophil accumulation to the lungs was increased in pancreatitis rats with LPS compared to that in non-pancreatitis ra … More ts with LPS.(4) In addition, myeloperoxidase activity in the lung was significantly increased in pancreatitis rats with LPS.(5) Superoxide production of brochoalveolar macrophages determined by in situ nitro blue terazolium (NBT) method was also enhanced in pancreatis rats with LPS.(6) Liver dysfucntinos were predominantly noted in pancreatitis rats with LPS, serologically and histologically.The survival rates during 24 hours in pancreatitis rats with LPS was significantly shorter than those in non-pancreatitis rats with LPS.The administration of protease inhibitors tends to decrease cytokine production and liver dysfunction in pancreatitis rats with LPS.Thus, hypercytokinemia and remote organ failures were encountered in pancreatitis rats when endotoxemia was involved. In cerulein-induced acute pancreatitis, macrophages could be primed and activated to release a large amount of cytokines when LPS was administared as the second attack. As a result, neutrphils accumulated into the remote organs leading to the tissue destruction. The administation of protease inhibitors trends to ameliorate these organ faulires. However, futrther experiments were required. Less