Effects of dexamethasone pretreatment on expression of matrix metalloproteinase-9 in rats with acute lung injury induced by phosgene

Abstract

To investigate the effects of dexamethasone on expression of matrix metalloproteinase-9 (MMP-9) in rats with acute lung injury induced by phosgene. The rats were randomly divided into 3 groups: normal control group that consists of the rats with air exposure, phosgene group that consists of the rats with phosgene exposure and dexamethasone group that consists of the rats with phosgene exposure after 2.5 mg/kg dexamethasone being injected. Wet and dry ratio of the lung (W/D) was calculated, and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded at 2 h after exposure. The concentrations of MMP-9 in the serum and BALF were measured by enzyme-linked immunosorbent assay. The pathologic changes of lung tissues were observed under light microscopy. The immunohistochemistry and the RT-PCR were used to detect the contents of MMP-9 in the lung tissue. Compared with phosgene group, the lung W/D, protein content and WBC count in of BALF dexamethasone group was significantly decreased (P < 0.01). MMP-9 levels of the serum and BALF in dexamethasone group were (4.799 +/- 0.043) microg/L and (15.052 +/- 0.029) microg/L, respectively, which were significantly lower than those [(9.439 +/- 0.100) and (20.640 +/- 0.446) microg/L] in phosgene group (P < 0.01). Compared with phosgene group (2.789 +/- 0.282),the expression level (1.183 +/- 0.260) of lung MMP-9 mRNA in dexamethasone group was significantly lower than that in phosgene group (P < 0.01). Histological experimental results showed the marked hyperemia and thickening of alveolar walls and stroma cells infiltrating and more visible alveolar structure damage of alveolar walls in phosgene group while the alveolar structure and the alveolar walls were clear and slightly thickened with inflammatory cells in dexamethasone group. Immunohistochemical results showed that MMP-9 protein expression levels of lung and bronchus tissues in normal control group and dexamethasone group were weakly positive, which in phosgene group were strongly positive. Dexamethasone has a beneficial effects on acute lung injury induced by phosgene in rats due to the inhibiting MMP-9.