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中性粒细胞在雨蛙素诱导的大鼠急性胰腺炎加重中的作用。这些介质可能导致多器官功能衰竭。1.体外培养的雨伞素性胰腺炎大鼠腹腔巨噬细胞经脂多糖刺激后产生的肿瘤坏死因子-α明显高于未感染的对照组。2.非胰腺炎大鼠的胰腺炎经腹腔注射内毒素作为败血症的激发。(1)胰腺炎合并内毒素感染的大鼠血清中肿瘤坏死因子-α的水平显著高于非胰腺炎合并内毒素感染的大鼠。(2)体外培养的胰腺炎大鼠肺泡巨噬细胞产生的肿瘤坏死因子-α显著高于单纯内毒素感染的大鼠(3)非胰腺炎大鼠肺组织中性粒细胞聚集明显高于非胰腺炎大鼠(…)。(4)此外，内毒素胰腺炎大鼠肺组织髓过氧化物酶活性显著升高。(5)原位硝基蓝四氮唑蓝(NBT)法检测，内毒素胰腺炎大鼠肺泡巨噬细胞超氧化物歧化生成增加。(6)从血清学和组织学角度看，内毒素胰腺炎大鼠主要表现为肝功能紊乱。内毒素胰腺炎大鼠24小时存活率明显短于非胰腺炎大鼠。给予蛋白酶抑制剂有减少细胞因子产生和肝功能障碍的趋势。内毒素血症时，胰腺炎大鼠出现高细胞分裂素血症和远隔器官衰竭。在雨蛙素诱导的急性胰腺炎中，当给予内毒素作为第二次攻击时，巨噬细胞可被激活并释放大量细胞因子。结果，中性粒细胞聚集到遥远的器官中，导致组织破坏。应用蛋白水解酶抑制剂有改善这些器官缺陷的趋势。然而，还需要进一步的实验。较少

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