Hypoxemia Induced the Changing Structure of the Lung Tissue in SD Rat Though Changing Blood Clotting and the Effects of Breviscapine’s Intervention

Objective To investigate the expressions of plasminogen activator inhibitor-1 (PAI-1), activated protein C (APC) and the histology structures of the rat lung tissues in the different hypoxia time; and to investigate the effects of breviscapine to the above changes. Methods Eighty SD rats were randomly divided into A (control), B (hypoxia), C (hypoxia+low-dose breviscapine) and D (hypoxia+high-dose breviscopine) groups with 20 rats in each group. Each hypoxia group placed daily pressure (101 kpa, 10% O2) environment for 8 h, low-dose and high-dose breviscapine groups were given of 10 mg/kg, 40 mg/kg breviscapine by intraperitoneal injection. On the 3^rd,7^th,14^th and 21^st d, 5 rats were randomly taken from each group and were killed for examination. The hematoxylin and eosin stain (HE stain) was performed for observation on pathological changes in the rat lung tissues. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for detection of the mRNA levels of transforming growth factor (TGF-β1) and Plasminogen activator inhibitor-1 (PAI-1). Western blot analysis was applied for detection of the expression of PAI-1. Besides, APC in the bronchoalveolar lavage fluid (BALF) was determined by ELISA. Results ① The HE stain demonstrated that compared with A group, the degree of thickening of alveolar septal the mRNA expressions of TGF-β1 and PAI-1, and the protein expressions of PAI-1 in B group were increased (P<0.05), and the expression of APC in the BALF was decreased (P<0.05). And with prolonged hypoxia, the more significant of these changes were observed. Positive correlation was found between the mRNA levels of PAI-1 and TGF-β1 (r=0.936, P<0.05). ② Compared with B group, the increased thicknesses of alveolar septal in C and D groups were lightened, the mRNA expressions of TGF-β1 and PAI-1, and the protein expression of PAI-1 were decreased (P<0.05), and the expressions of APC in the BALF was increased (P<0.05).With increasing dose, the expression levels of each factor gradually reduced or increased. Conclusion Hypoxia may cause coagulant function abnormality to increase clotting activity and reduce fibrinolytic activity and the anticoagulant activity, inducing alveolar septal thickening, and the mechanism of above changes may related to the TGF-β1 signaling pathways. Breviscapine could improve hypoxia-induced hypercoagulable state that alleviate alveolar septal thickening.