European journal of gastroenterology & hepatology · 1995
Alpha-1-antichymotrypsin is an effective inhibitor of pancreatitis-induced lung injury.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
O'Donovan D A, Kelly C J, Bouchier-Hayes D M, Grace P, Redmond H P, Burke P E, Bouchier-Hayes E J
Аннотация
BACKGROUND: Pancreatitis-induced adult respiratory distress syndrome (ARDS) may result from an imbalance between leucocyte proteases, produced by infiltrating neutrophils, and endogenous protease inhibitors.
OBJECTIVE: The aim of this study was to evaluate the role of recombinant alpha-1-antichymotrypsin (rACT P3-P3'), an endogenous serine protease inhibitor, in ameliorating lung injury associated with pancreatitis.
DESIGN: Sprague-Dawley rats were randomly divided into control (saline infusion) and pancreatitis groups, which were treated immediately with saline or rACT P3-P3' (50 mg/kg body weight).
METHODS: Myeloperoxidase (MPO) was employed as a monitor of neutrophil traffic in the lung, and wet-dry lung weights as a measure of pulmonary endothelial permeability. Lungs were also evaluated histologically.
RESULTS: Caerulein (5 micrograms/kg body weight/h) induced pancreatitis in all animals, with an increase in serum amylase from 1851 +/- 208 IU (control) to 5198 +/- 924 IU (pancreatitis), P < 0.05. Pancreatitis caused a significant increase in MPO activity (7.8 +/- 1.1 units compared with 2.08 +/- 0.5 units in controls, P < 0.001) and wet-dry lung weight ratios (12.8 +/- 3.3 compared with 3.2 +/- 0.1 in controls, P < 0.001), indicating significant pulmonary neutrophil influx and microvascular leakage, respectively. These increases in MPO activity and wet-dry ratios were decreased in the pancreatitis group treated with rACT P3-P3' (MPO 4.68 +/- 0.7 units, wet-dry ratio 4.2 +/- 0.5, P < 0.05 compared with the untreated pancreatitis group).
CONCLUSION: These data support the hypothesis that deficient endogenous protease inhibition may be responsible for the neutrophil-mediated lung injury observed in pancreatitis and suggest that there may be a therapeutic role for recombinant protease inhibitors such as alpha-1 antichymotrypsin.
OBJECTIVE: The aim of this study was to evaluate the role of recombinant alpha-1-antichymotrypsin (rACT P3-P3'), an endogenous serine protease inhibitor, in ameliorating lung injury associated with pancreatitis.
DESIGN: Sprague-Dawley rats were randomly divided into control (saline infusion) and pancreatitis groups, which were treated immediately with saline or rACT P3-P3' (50 mg/kg body weight).
METHODS: Myeloperoxidase (MPO) was employed as a monitor of neutrophil traffic in the lung, and wet-dry lung weights as a measure of pulmonary endothelial permeability. Lungs were also evaluated histologically.
RESULTS: Caerulein (5 micrograms/kg body weight/h) induced pancreatitis in all animals, with an increase in serum amylase from 1851 +/- 208 IU (control) to 5198 +/- 924 IU (pancreatitis), P < 0.05. Pancreatitis caused a significant increase in MPO activity (7.8 +/- 1.1 units compared with 2.08 +/- 0.5 units in controls, P < 0.001) and wet-dry lung weight ratios (12.8 +/- 3.3 compared with 3.2 +/- 0.1 in controls, P < 0.001), indicating significant pulmonary neutrophil influx and microvascular leakage, respectively. These increases in MPO activity and wet-dry ratios were decreased in the pancreatitis group treated with rACT P3-P3' (MPO 4.68 +/- 0.7 units, wet-dry ratio 4.2 +/- 0.5, P < 0.05 compared with the untreated pancreatitis group).
CONCLUSION: These data support the hypothesis that deficient endogenous protease inhibition may be responsible for the neutrophil-mediated lung injury observed in pancreatitis and suggest that there may be a therapeutic role for recombinant protease inhibitors such as alpha-1 antichymotrypsin.