肺纤维化支气管肺泡灌洗液凝血及纤溶指标的变化

目的:测定肺纤维化大鼠支气管肺泡灌洗液(BALF)中凝血及纤溶指标的水平,探讨其在诊断肺纤维化中的作用.方法:36只SD大鼠随机分为2组,每组各18只,分别向气管内滴入博莱霉素A5(BLMA5)5 mg/kg 和生理盐水建立肺纤维化和对照组模型,造模后第7、14、28天测定BALF中标准血浆的复钙时间以了解促凝活性(procoagulation activity, PCA)、血管性血友病因子(von Willebrand factor, vWF)含量、抗凝血酶Ⅲ(antithrombin-Ⅲ, AT-Ⅲ)、纤溶酶原激活剂抑制物-1(plasminogen activity inhibitor-1, PAI-1)和尿激酶型纤溶酶原激活剂(urokanise-type plasminogen activator ,uPA)的活性.结果:(1)实验组各时间点复钙时间分别为(56±10),(78±3)和(172±11) s,对照组分别为(190±10),(186±8),(184±6) s,两组比较除第28天外差异均有统计学意义(P＜0.01);(2)各时间段两组vWF含量、AT-Ⅲ活性差异均无统计学意义;(3)BLM组BALF 中各时间段PAI-1的活性分别为(1.04±0.08),(1.47±0.06),(3.03±0.18) u/mL,对照组分别为(0.66±0.11),(0.71±0.09),(0.70±0.08) u/mL,同一时间两组间比较差异均有统计学意义(P＜0.01);(4)BLM组BALF 中uPA的活性分别为(0.19±0.03),(0.16±0.02),(0.12±0.05) u/mL,对照组分别为(0.26±0.05),(0.25±0.06),(0.24±0.07)u/mL,同一时间两组间比较差异均有统计学意义(P＜0.01).结论:PCA升高可以作为判断早期肺泡炎的方法.PAI-1活性升高及uPA活性减低使纤溶活性持续受损,可作为判断早期肺纤维化和反映其严重程度的指标.vWF和AT-Ⅲ对诊断肺纤维化无意义.

Changes of coagulation and fibrinolysis system in bronchoalveolar lavage fluid in lung fibrosis

OBJECTIVE: To investigate the activity of coagulation and fibrinolysis systems in bronchoalveolar lavage fluid (BALF) in lung fibrosis in rats, and to study their role in diagnosis of lung fibrosis. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into 2 groups (n=18 in each group ). Lung fibrosis and control models were made by tracheal instillation bleomycinA(5) (BLMA(5)) (5 mg/kg) and saline. On days 7, 14 and 28, the recalcification time points of normal pooled plasma for studying procoagulation activity (PCA), the levels of von Willebrand Factor (vWF), the activities of Antithrombin-III(AT-III) , plasminogen activity inhibitor-1 (PAI-1) and urokanise-type plasminogen activator (uPA) in BALF were measured respectively. RESULTS: (1) In BLM group,the recalcification time points in BALF were (56+/-10), (78+/-3) and (172+/-11) seconds respectively, they were (190+/-10), (186+/-8) and (184+/-6) seconds respectively in control group. The difference was significant (P<0.01) except on day 28; (2) The differences in level of vWF and activity of AT-III in BALF were not significant in BLM group versus control group; (3) Activities of PAI-1 in BALF in BLM group were (1.04+/-0.08), (1.47+/-0.06), (3.03+/-0.18) u/mL respectively, while they were (0.66+/-0.11), (0.71+/-0.09), (0.70+/-0.08) u/mL respectively in control group. The difference was significant (P<0.01); (4) Activities of uPA in BALF in BLM group were (0.19+/-0.03), (0.16+/-0.02), (0.12+/-0.05) u/mL respectively, while they were (0.26+/-0.05), (0.25+/-0.06), (0.24+/- 0.07) u/mL respectively. The difference was significant (P<0.01). CONCLUSION: The PCA upregulation might be means to diagnose alveolitis. The activity of the fibrinolysis system was injured progressively by PAI-1 activity upregulation and uPA activity downregulation, which might be taken as means to study the occurrence of early lung fibrosis and its development,vWF and AT-III rendered no help in diagnosis of lung fibrosis.