Stringer K A, Hybertson B M, Cho O J, Cohen Z, Repine J E
Department of Pharmacy Practice, School of Pharmacy, Denver, CO 80262, USA.
Free Radic Biol Med. 1998 Jul 15;25(2):184-8. doi: 10.1016/s0891-5849(98)00047-1.
Because plasminogen activators (PA) may participate in the inflammatory process associated with the acute respiratory distress syndrome (ARDS), we measured the effect of tissue plasminogen activator (tPA) on inflammation and acute lung leak caused by intratracheal instillation of IL-1alpha (50 ng) into male (300-400 g) Sprague-Dawley rats. Lung leak, lung myeloperoxidase (MPO) activity, and lung lavage neutrophil counts were increased in rats given IL-1 intratracheally compared to control rats that were given saline intratracheally. Giving tPA (12 mg/kg) intraperitoneally increased lung tPA concentration and reduced acute lung leak in rats given IL-1 intratracheally (p < .01; lung leak index for sham-treated rats: 0.040 + 0.001, n=6; IL-1: 0.10 + 0.01, n=10; tPA + IL-1: 0.050 + 0.002, n=6). In contrast, administering tPA did not change IL-1-induced increases in lung lavage neutrophils or lung MPO activity (sham: 0.003 x 106 + 0.001 x 10(6) cells; IL-1: 2.9 x 10(6) + 0.4 x 10(6) cells; tPA + IL-1: 2.7 x 10(6) + 0.4 x 10(6) cells; and sham: 0.6 + 0.2 U/g lung; IL-1: 11.2 + 2.9 U/g lung, tPA + IL-1: 11.1 + 1.6 U/g lung, respectively). Our results suggest that intraperitoneal tPA administration increases lung tissue tPA levels and decreases acute lung leak without reducing lung neutrophil infiltration in rats given IL-1alpha intratracheally. This work suggests that tPA may suppress neutrophil activation in vivo and accordingly have anti-inflammatory effects.
由于纤溶酶原激活剂（PA）可能参与与急性呼吸窘迫综合征（ARDS）相关的炎症过程，我们测定了组织纤溶酶原激活剂（tPA）对雄性（300 - 400克）Sprague-Dawley大鼠气管内注入IL-1α（50纳克）所引起的炎症和急性肺渗漏的影响。与气管内注入生理盐水的对照大鼠相比，气管内给予IL-1的大鼠肺渗漏、肺髓过氧化物酶（MPO）活性和肺灌洗中性粒细胞计数增加。腹腔内给予tPA（12毫克/千克）可增加气管内给予IL-1的大鼠肺组织tPA浓度并减少急性肺渗漏（p < 0.01；假处理大鼠的肺渗漏指数：0.040 + 0.001，n = 6；IL-1组：0.10 + 0.01，n = 10；tPA + IL-1组：0.050 + 0.002，n = 6）。相比之下，给予tPA并未改变IL-1诱导的肺灌洗中性粒细胞或肺MPO活性的增加（假处理组：0.003×10⁶ + 0.001×10⁶个细胞；IL-1组：2.9×10⁶ + 0.4×10⁶个细胞；tPA + IL-1组：2.7×10⁶ + 0.4×10⁶个细胞；假处理组：0.6 + 0.2单位/克肺；IL-1组：11.2 + 2.9单位/克肺，tPA + IL-
