Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion
Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion
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DOI：
10.1097/01.shk.0000142253.31006.8c
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发表时间：
2004-11-01
期刊：
影响因子：
3.1
通讯作者：
Schmid-Schönbein, GW
中科院分区：
文献类型：
--
作者：
Ishimaru, K;Mitsuoka, H;Schmid-Schönbein, GW
缺血肠中的胰酶参与体内炎症介质的产生。这些介质在休克期间刺激心血管系统的细胞并引发多器官衰竭。控制炎症程度的一个重要方面是这些介质从缺血肠的分散。在过去，已经确定了这些炎症介质的两种分散途径，吸收到肠静脉循环和吸收到淋巴管。我们在此假设，肠腔内胰腺消化酶产生的炎症介质也可能直接释放到腹膜间隙。为了评估炎症介质在腹腔内对内脏动脉闭塞（90分钟）和再灌注（SAO休克）的反应，我们测量了从腹腔收集的液体激活原始供体粒细胞的能力。对照大鼠SAO后，腹腔灌洗液在体外实验中引起原始供体粒细胞的活化。相反，当用广谱胰酶抑制剂（6-氨基-2-萘基对胍苯甲酸二甲磺酸酯）冲洗小肠管腔时，液体不再引起白细胞活化。腹膜液中炎症介质水平的降低与SAO休克后血压下降的衰减有关。这些结果表明，由胰腺消化酶产生的炎症介质可以通过经腹腔途径直接被吸收进入体循环，并在多器官衰竭的发展中发挥作用。
Pancreatic enzymes in the ischemic intestine are involved in the production of in vivo inflammatory mediators. These mediators stimulate cells in the cardiovascular system during shock and initiate multiorgan failure. An important aspect that controls the extent of the inflammation is the dispersion of these mediators from the ischemic intestine. In the past, two pathways for dispersion of these inflammatory mediators have been identified, absorption into the intestinal venous circulation and uptake into the lymphatics. We hypothesize here that the inflammatory mediators produced by pancreatic digestive enzymes in the lumen of the intestine may also be released directly into the peritoneal space. To assess the presence of inflammatory mediators in the peritoneal cavity in response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock), we measured the ability of fluid collected from this cavity to activate naive donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused activation of naive donor granulocytes when tested in vitro. In contrast, when the lumen of the small intestine was flushed with a broad-acting pancreatic enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the fluid no longer caused leukocyte activation. Reduction of the levels of inflammatory mediators in the peritoneal fluid was associated with an attenuation in the fall of blood pressure after SAO shock. These results indicate that the inflammatory mediators, which are produced by pancreatic digestive enzymes, can be absorbed directly into the systemic circulation via a transperitoneal route and play a part in the development of multiorgan failure.