[The change and significance of coagulation activity in bleomycin-induced lung fibrosis in rats].
OBJECTIVE: To investigate the role of coagulation activity of bronchoalveolar lavage fluid (BALF) in the pathogenesis of lung fibrosis. METHODS: Fourty-eight Sprague-Dawley rats were randomly divided into 2 groups, 24 rats in each group. In the bleomycin (BLM) group, the lung fibrosis model was made by tracheal instillation of bleomycin A(5) (BLMA(5), 5 mg/kg). At day 7, 14, 28 and 40, the recalcification time of normal pooled plasma, factor VII and X deficiency plasma were measured for procoagulation activity (PCA), and the thrombin activity and the protein level of transforming growth factor beta(1) (TGF-beta(1)) in BALF were also measured. In the control group, normal solution was instillated into the lungs. RESULTS: In the BLM group, the recalcification time of normal pooled plasma in BALF at the four time points were (56 +/- 10), (78 +/- 4), (172 +/- 11) and (180 +/- 6) s respectively, while in the control group, were (190 +/- 10), (186 +/- 8), (184 +/- 6) and (185 +/- 6) s respectively. The thrombin activity at the four time points were (1.26 +/- 0.03), (0.82 +/- 0.05), (0.28 +/- 0.03) and (0.28 +/- 0.02) microg/ml respectively in the BLM group, but were (0.31 +/- 0.02), (0.32 +/- 0.03), (0.31 +/- 0.04) and (0.29 +/- 0.05) microg/ml respectively in the control group. The level of TGF-beta(1) at the four time points were (310 +/- 36), (220 +/- 30), (109 +/- 12) and (96 +/- 11) ng/ml respectively in the BLM group, but were (92 +/- 20), (94 +/- 12), (92 +/- 10) and (90 +/- 9) ng/ml respectively in the control group. The above measurements were significantly different in day 7 and 14 between the BLM group and the control group (P < 0.01), while the differences were not significant at day 28 and 40 (P > 0.01). In the BLM group, at day 7 and 14, the recalcification time of factor VII deficiency plasma was (123 +/- 12) and (162 +/- 4) s respectively; the recalcification time of factor X deficiency plasma was (357 +/- 22) and (387 +/- 12) s respectively; the recalcification time of factor X deficiency plasma was longer than that of factor VII deficiency plasma and that of normal pooled plasma. Within 14 day, the level of TGF-beta(1) was positively correlated with PCA and thrombin activity. CONCLUSIONS: During the period of alveolitis, the PCA and thrombin activity were upregulated in BALF, which was caused by activated factor VII activating factor X and the switching to the exogenous coagulation pathway. But during the period of lung fibrosis, their activities were not upregulated. These results suggest that the coagulation factor and thrombin might contribute to the development of pulmonary fibrosis by promoting production of TGF-beta(1).