Changes of Activities of Gelatinases in Bronchoalveolar Lavage Fluid from Rats with Lipopolysaccaride-induced Acute Lung Injury

Objective:To investigate the role of gelatinases in the pathogenesis of acute lung injury (ALI) induced by lipopolysaccaride (LPS). Methods:Thirty-two rats were randomly divided into saline control group and different LPS groups (2 h, 4 h and 6 h after LPS challenge). Lung injury was quantified by measurements of PaO 2/FiO 2, lung permeability index (LPI) and histopathologic scoring. Samples obtained from bronchoalveolar lavage (BAL) fluid were compared for the presence of gelatinases by gelatin zymography. Immunohistochemical staining of the type-Ⅳ collagen was performed on sections of lung specimens. Results: The animals treated with LPS for 4 h and 6 h had developed ALI with respiratory failure as evidenced by a decrease of PaO 2/FIO 2 and an increase of LPI and histopathologic total lung injury score (all P0.01 versus the control group). MMP-2 (gelatinase A) activity was significantly increased at 2nd h after LPS (P 0.01 versus the control group), and not further changed at 4th h or 6th h after LPS (P0.05 versus 2 h group). MMP-9 (gelatinase B) was not essentially detectable in rats treated with saline, but great in rats treated with LPS for 2 h, and further enhanced at 4th h and 6th h after LPS (P0.01 versus 2 h group). MMP-9 activity was significantly correlated with PaO 2/FiO 2, LPI and the histopathologic total lung injury score (r=-0.69, r=0.80, r=0.71, respectively, all P0.05). MMP-2 activity had a correlation with the histopathologic total lung injury score (r=0.50, P0.05 ). Staining for type Ⅳ collagen showed the basement membrane (BM) in lung tissue was disrupted by LPS whereas no disruption was detected in the control group. Conclusion:Gelatinases (MMP-2 and MMP-9) play a role in the pathogenesis of LPS-induced acute lung injury, at least in part, through the degradation of the basement membrane in lung tissue.