Idell Steven, Jun Na Moon, Liao Huai, Gazar A E, Drake Wonder, Lane Kirk B, Koenig Kathy, Komissarov Andrey, Tucker Torry, Light Richard W
The Texas Lung Injury Institute, The University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
Exp Lung Res. 2009 Oct;35(8):665-81. doi: 10.3109/01902140902833277.
Intrapleural fibrin deposition and subsequent fibrosis characterize evolving empyema and contribute to the morbidity associated with this condition. Single-chain urokinase (scuPA) is proenzyme form of the urokinase plasminogen activator, which has recently been shown to effectively clear intrapleural loculation in tetracycline-induced pleurodesis in rabbits. The authors therefore hypothesized that scuPA could likewise improve intrapleural injury associated with empyema. The authors used a rabbit model of empyema induced by intrapleural administration of Pasturella multocida to test this hypothesis and determined the effects of intrapleural scuPA on pleural fluids indices of inflammation and intrapleural fibrosis. The authors found that intrapleural administration of scuPA was well tolerated, generated readily detectable fibrinolytic activity in the empyema fluids and did not induce intrapleural or systemic bleeding. Pleural fluid volume, intrapleural protein, and D-dimer concentrations were increased at 24 and 48 hours (P < .01, respectively) after induction of empyema. Intrapleural loculation did not occur in the scuPA- or vehicle control-treated animals and there was no significant change in the pleural empyema or thickening scores. These findings confirm that intrapleural scuPA generates fibrinolysis in empyema fluids but does not alter fibrotic repair at the pleural surface or the intensity of intrapleural inflammation in this empyema model.
胸膜内纤维蛋白沉积及随后的纤维化是脓胸进展的特征,并导致与该病症相关的发病率。单链尿激酶(scuPA)是尿激酶型纤溶酶原激活剂的酶原形式,最近已证明其能有效清除兔四环素诱导的胸膜固定术中的胸膜内分隔。因此,作者推测scuPA同样可以改善与脓胸相关的胸膜内损伤。作者使用胸膜内注射多杀巴斯德菌诱导的兔脓胸模型来验证这一假设,并确定胸膜内注射scuPA对胸膜液炎症指标和胸膜内纤维化的影响。作者发现,胸膜内注射scuPA耐受性良好,在脓胸液中产生易于检测到的纤溶活性,且不会引起胸膜内或全身性出血。脓胸诱导后24小时和48小时,胸膜液体积、胸膜内蛋白和D-二聚体浓度增加(分别为P < .01)。在接受scuPA或赋形剂对照治疗的动物中未发生胸膜内分隔,胸膜脓胸或增厚评分也无显著变化。这些发现证实,胸膜内scuPA可在脓胸液中产生纤维蛋白溶解作用,但在该脓胸模型中不会改变胸膜表面的纤维化修复或胸膜内炎症的强度。