肺纤维化大鼠支气管肺泡灌洗液及血浆凝血、纤溶活性的变化

Changes of Coagulation and Fibrinolysis Activity in Bronchoalveolar Lavage Fluid and Plasma in Rats with Lung Fibrosis

目的测定肺纤维化大鼠支气管肺泡灌洗液(BALF)及血浆中凝血、纤溶指标的活性。方法36只SD大鼠随机分为博来霉素A5(BLMA5)组和对照组,每组各18只。大鼠气管内分别滴入BLMA5(5mg/kg)和生理盐水建立肺纤维化和对照组模型,于造模后7、14、28d分别测定BALF及血浆复钙时间以了解促凝活性(PCA)、血管性血友病因子(vWF)含量、纤溶酶原激活剂抑制物1(PAI1)的活性和D二聚体(D Dimer)的水平。结果①BLMA5组BALF复钙时间缩短,第7、14天复钙时间与对照组比较差异有极显著性意义(均P<0.01);BLMA5组血浆复钙时间与对照组比较差异无显著性意义(均P>0.05)。②BLMA5组BALF和血浆vWF含量与对照组比较差异均无统计学意义(均P>0.05)。③BLMA5组BALFPAI1活性较对照组明显增强(均P<0.01);BLMA5组血浆PAI1活性与对照组比较增强不明显(P>0.05)。④BLMA5组BALFD Dimer水平升高,第7、14天D Dimer水平与对照组比较,差异均有极显著性意义(均P<0.01);第7天BLMA5组血浆D Dimer水平与对照组比较,差异有极显著性意义(P<0.01)。结论肺纤维化存在凝血和纤溶活性的异常,凝血、纤溶活性的异常变化主要表现在BALF中。

Objective To determine coagulation and fibrinolysis activity in bronchoalveolar lavage fluid （BALF） and plasma of rats with 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 of bleomycinA5 （BLMA5, 5mg/kg） and saline respectively. At 7th, 14th, 28th day, the recalcification time of normal pooled plasma for studying procoagulation activity （PCA）, the level of yon Willebrand factor （vWF）, the activity of plasminogen activity inhibitor-1 （PAI-1） and the level of D-Dimer in BALF and plasma were measured. Results ① The recalcification time in BALF in BLMA5 group was significantly shortened at 7th and 14th day as compared with control gorup （P〈0.01） except 28th day, but in plasma, there was no significant difference between the two groups （P〉0.05）. ② There was no significant difference in the level of vWF in BALF and plasma between BLMA5 group and control group （P〉0.05）. ③ Activity of PAI-1 in BALF in BLMA5 group was significantly increased as compared with control group （all P〈0.01）, but there was no difference between the two groups in the plasma （P〈0.05）. ④ The level of D-Dimer in BALF was significantly increased in BLMA5 group at 7th and 14th day as compared with control group （both P〈0.01）, and at 7th day, there was significant difference in plasma D-Dimer level between BLMA5 group and control group （P〈0.01）. Conclusion The abnormal coagulation and fibrlnolysis activity exist in lung fibrosis. In BALF, the PCA and D-Dimer activity were upregulated in the alveolitis, but not in the fibrosis. PAI-1 activity was upregulated from alveolhis to fibrosis. Plasma D-Dimer was determined only in alveolitis.