Wang Hou-Hong, Tang A-Mao, Chen Li, Zhou Meng-Tao
Department of Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
Exp Lung Res. 2012 Nov;38(9-10):445-52. doi: 10.3109/01902148.2012.721860. Epub 2012 Sep 24.
The incidence of acute pancreatitis has been rising worldwide in the past few decades. Despite extensive research efforts, the population-based mortality from acute pancreatitis remains high. Since dysfunction of multiple vital organs, most importantly the lungs, is the major cause of early death in acute pancreatitis patients, developing effective strategies to manage lung injury has become one of the focuses of recent research efforts aiming at improving the outcome of patients with acute pancreatitis. In this study, we attempted to create a rat model of acute pancreatitis through intraductal infusion of taurocholate and to evaluate the potential of sivelestat, a synthetic neutrophil elastase inhibitor, in protection against acute pancreatitis-associated lung injury using this rat model. The results demonstrated that: (1) 5% sodium taurocholate successfully induced histopathologic and biochemical abnormalities in the circulation, lung and pancreas characteristic of human acute pancreatitis, including an increase in amylase concentration and a decrease in partial arterial oxygen pressure (PaO2) in the blood, increases in activities of myeloperoxidase (MPO) (a lung injury marker) and neutrophil elastase (a quantitative indicator of neutrophil infiltration), and levels of malondialdehyde (an indicator of lipid peroxidation) and tumor necrosis factor-alpha (a major inflammatory mediator) in the lung; (2) intravenous administration of sivelestat effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. Our findings have validated the taurocholate model of acute pancreatitis and demonstrated great therapeutic potential for sivelestat in managing acute pancreatitis-associated lung injury.
在过去几十年中，急性胰腺炎的发病率在全球范围内一直在上升。尽管进行了广泛的研究，但急性胰腺炎的人群死亡率仍然很高。由于多个重要器官功能障碍，尤其是肺部，是急性胰腺炎患者早期死亡的主要原因，因此制定有效的策略来管理肺损伤已成为近期旨在改善急性胰腺炎患者预后的研究重点之一。在本研究中，我们试图通过导管内注入牛磺胆酸盐建立急性胰腺炎大鼠模型，并使用该大鼠模型评估合成中性粒细胞弹性蛋白酶抑制剂西维来司他预防急性胰腺炎相关肺损伤的潜力。结果表明：（1）5%牛磺胆酸钠成功诱导了具有人类急性胰腺炎特征的循环、肺和胰腺的组织病理学和生化异常，包括血液中淀粉酶浓度升高和动脉血氧分压（PaO2）降低；肺中髓过氧化物酶（MPO）（一种肺损伤标志物）和中性粒细胞弹性蛋白酶（中性粒细胞浸润的定量指标）的活性增加，以及丙二醛（脂质过氧化指标）和肿瘤坏死因子-α（一种主要炎症介质）水平升高；（2）静脉注射西维来司他有效地减轻了牛磺胆酸盐诱导的除血清淀粉酶浓度外所有分析参数的异常。我们的研究结果验证了急性胰腺炎的牛磺胆酸盐模型，并证明了西维来司他在管理急性胰腺炎相关肺损伤方面具有巨大的治疗潜力。
