实验性肺血栓栓塞症后凝血纤溶系统及肺血管内皮功能变化的临床意义

目的　探讨实验性兔肺血栓栓塞症 (PTE)后凝血纤溶系统、肺血管内皮功能的变化及其临床意义 ,了解尿激酶对凝血纤溶系统及肺血管内皮功能的影响。方法　 2 4只雄性新西兰大耳白兔随机分为正常对照组、单纯栓塞组及尿激酶组 ,每组 8只。单纯栓塞组及尿激酶组经兔股静脉注入自体血凝块制备兔PTE模型。尿激酶组用尿激酶治疗动态观察尿激酶治疗前后兔凝血纤溶系统活性和血浆中内皮素 1(ET 1)、一氧化氮 (NO)、血管性血友病因子 (vWF)的变化。结果　解剖肺脏栓塞部位肉眼观 ,见肺表面点片状出血灶 ;镜下肺动脉血管内可见注入的血凝块与继发的血栓形成 ,肺泡周围有大量炎性细胞浸润 ,肺泡和间质内有局灶出血。肺栓塞后血D 二聚体 (D dimer)、ET 1、vWF水平明显增高 ,而组织型纤溶酶原激活剂 (t PA)、NO、抗凝血酶Ⅲ (AT Ⅲ )水平明显下降 (P <0 0 5 )。PTE兔经尿激酶治疗后肺脏病理改变减轻 ,D dimer水平在栓塞后 1及 2h高于栓塞前 (P <0 0 5 ) ,4h后降至栓塞前水平 ;t PA、NO及AT Ⅲ在肺栓塞后低于栓塞前 (P <0 0 5 ) ;ET 1在栓塞后 2h高于栓塞前(P <0 0 5 ) ,4h降至栓塞前水平。结论　PTE对体内凝血纤溶系统及肺血管内皮功能均有重要影响。PTE兔经尿激酶溶栓治疗可维持机体凝血纤溶系统的平衡及保护肺血

Study of the function of coagulation,fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits

OBJECTIVES: To study the functional changes and the significance of coagulation, fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits. METHODS: Rabbit pulmonary thromboembolism models by injection of auto-blood clots into femoral vein were used to observe the dynamical changes of activity of coagulation and fibrinolysis and endothelin-1 (ET-1), nitrogen monoxide (NO), von Willebrand factor (vWF) in blood. RESULTS: Petechial and patchy hemorrhages were observed on the surfaces of embolic lungs. The injected blood clots and secondary thrombosis in the pulmonary arteries, inflammatory cell infiltration around alveoli, local hemorrhages in the alveoli and interstitial tissue could be found by microscopy. The concentration of D-dimer, ET-1 and vWF in blood were significantly elevated, and the tissue-type plasminogen activator (t-PA), NO and antithrombin III (AT-III) decreased significantly after embolism (P < 0.05). After administration of urokinase, the pathological injuries relieved, and the concentration of D-dimer was higher at 1 h and 2 h after embolization than that before embolization (P < 0.05), and reduced to the level of pre- embolization at 4 h after embolization. The levels of t-PA, NO and AT-III after embolization were lower than those before embolization (P < 0.05). The level of ET-1 was higher at 2 h after embolization (P < 0.05) and reduced to the level of pre-embolization at 4 h. CONCLUSIONS: PTE has important impacts on coagulation, fibrinolysis and pulmonary vascular endothelial function. Thrombolysis with urokinase could keep the balance between coagulation and fibrinolysis and protect pulmonary vascular endothelial function.