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

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。

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

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 PAI-1 activity in bronchoalveolar lavage fluid(BALF) were also detected.Meanwhile,pulmonary histological scoring was performed for ALI evaluation.Results PAI-1 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 PAI-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.