Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis
Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis
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DOI：
10.1097/01.ccm.0000049948.64660.06
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发表时间：
2003-02-01
影响因子：
8.8
通讯作者：
Closa, D
中科院分区：
文献类型：
--
作者：
Granell, S;Gironella, M;Closa, D
目的：探讨低分子肝素对急性胰腺炎患者血浆黄嘌呤氧化酶浓度及肺部炎症反应的影响。设计：随机对照试验。设置：实验室。实验对象：雄性Wistar大鼠。干预：急性胰腺炎是由导管内给药5%牛磺胆酸钠引起的。诱导胰腺炎后立即给予低分子量肝素（0、30、90或300单位/kg）。测量方法及主要结果：胰腺炎诱导后3小时测定脂肪酶和黄嘌呤氧化酶血浆浓度。测定肺组织中p -选择素信使RNA的表达和作为中性粒细胞浸润标志的髓过氧化物酶活性。胰腺炎期间观察到黄嘌呤氧化酶血浆浓度升高。在对照组和胰腺炎动物中，肝素也增加了血浆黄嘌呤氧化酶的活性。黄嘌呤氧化酶存在于内皮表面的测量表明，在胰腺炎期间，酶从胃肠道内皮释放。相比之下，肝素可以动员几乎所有器官的黄嘌呤氧化酶。胰腺炎时肺中性粒细胞浸润增加。肝素进一步以剂量依赖的方式增加了胰腺炎动物肺中髓过氧化物酶活性和p -选择素的表达。相比之下，在对照动物中，肝素对髓过氧化物酶活性没有影响，也没有诱导p-选择素上调。结论：在急性胰腺炎期间，肝素可能调动附着在内皮细胞上的黄嘌呤氧化酶，在循环中形成自由基生成系统，从而引发肺部炎症反应。
Objective: To evaluate the effect of low molecular weight heparin on plasma xanthine oxidase concentrations and lung inflammatory response during acute pancreatitis.Design: Randomized, controlled trial.Setting: Experimental laboratory.Subjects: Male Wistar rats.Interventions: Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Low molecular weight heparin (0, 30, 90, or 300 units/kg) was administered immediately after induction of pancreatitis.Measurements and Main Results: Lipase and xanthine oxidase plasma concentrations were measured 3 hrs after pancreatitis induction. Expression of P-selectin messenger RNA and myeloperoxidase activity as a marker of neutrophil infiltration were determined in, the lung. An increase in xanthine oxidase plasma concentrations was observed during pancreatitis. Administration of heparin also increased plasma xanthine oxidase activity in both control and pancreatitis animals. Measures of xanthine oxidase present in the endothelial surface indicate that during pancreatitis, the enzyme is released from the gastrointestinal endothelium. By contrast, heparin mobilizes xanthine oxidase from almost all organs evaluated. Neutrophil infiltration was increased in the lung during pancreatitis. Heparin administration further increased, in a dose-dependent manner, myeloperoxidase activity and P-selectin expression in the lung in animals with pancreatitis. By contrast, in control animals, heparin had no effect on myeloperoxidase activity and did not induce P-selectin up-regulation.Conclusion: During acute pancreatitis, heparin administration might mobilize xanthine oxidase attached to endothelial cells, originating a free radical-generating system in the circulation that would trigger an inflammatory response in the lung.