急性肺损伤时纤溶酶原激活物抑制剂-1活性变化和尿激酶对其变化的影响

Changes of plasminogen activator inhibitor-1 activity and effects of exogenous urokinase on endotoxinin-duced acute lung injury

目的观察内毒素诱导幼猪急性肺损伤时纤溶酶原激活物抑制剂(PAI)-1活性的变化;了解尿激酶对这种变化的影响。方法17只4周龄小白猪随机分3组:盐水(NS)对照组5只,内毒素(LPS)组6只,尿激酶(UK)组6只。测定基础状态,急性肺损伤成模时,成模后2 h、4 h、6 h血浆PAI-1活性,成模6 h后测定支气管肺泡灌洗液(BALF)中白细胞计数、总蛋白含量和PAI-1活性,肺湿干重比,并做病理评分。结果PAI-1活性在LPS组成模后增高,UK组在成模4、6 h较LPS组下降(P<0.05)。BALF中白细胞计数和肺组织病理评分在LPS组较NS组增高,UK组较LPS组降低(P<0.05)。BALF中PAI-1活性在LPS组和UK组较NS组增高(P<0.05),UK组较LPS组有降低趋势(P>0.05)。结论LPS诱导幼猪急性肺损伤时存在PAI-1活性增高,尿激酶可改善这种纤溶抑制状态,减少肺泡白细胞渗出,减轻肺组织损伤,对急性肺损伤有保护作用。

Objective To observe the changes of plasminogen activator inhibitor-1 （PAI-1） activity and to evaluate therapeutic effect of exogenous urokinase （ UK ） on endotoxin-induced acute lung injury （ALI）. Methods Seventeen healthy one-month-old piglets were randomly divided into three groups： normal saline control （NS） group （ n = 5）, LPS group （ n = 6） and UK group （ n = 6）. PAI-1 activity was detected at baseline, 0, 2, 4, 6 h of ALI. At the end of the experiment, all piglets were sacrificed and lungs were removed for bronchoalveolar lavage and lung wet-to-dry （W/D） weight measurement. Total leukocyte number, protein concentration and PAL 1 activity in bronchoalveolar lavage fluid （BALF） were also detected. Meanwhile, pulmonary histological scoring was performed for ALI evaluation. Results PAL1 activity of LPS groups increased after ALI. At the time point of 4 h and 6 h, PAI 1 activity of UK group were lower than that of LPS group （P 〈 0.05）. In LPS group, the BALF leukocyte count and the histopathological lung injury score were significantly higher than those in NS group （P〈 0.05）. In contrast to LPS group, UK group showed less obvious changes after treatment （P 〈 0.05）. BALF PAL-1 activity of LPS group and UK group were markedly higher than that of NS group （P 〈 0.05）. Furthermore, there was a trend of decline in UK group, in contrast to the LPS group （P〉0.05）.Conclusion PAI-1 activity was increased in endotoxin-induced acute lung injury of piglets. The UK can be used to relieve the fibrinolytic inhibition of ALI, diminish the leukocytic infiltration and reduce lung injury.