Inhibition of matrix metalloproteinase-9 with low-dose doxycycline reduces acute lung injury induced by cardiopulmonary bypass.

OBJECTIVE This study aims to demonstrate the protective effect of doxycycline, an exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), in the acute lung injury induced by cardiopulmonary bypass (CPB). METHODS A total of 30 healthy mongrel dogs were randomly divided into three groups: Group A (CPB control group, no treatment of doxycycline), Group B (low-dose group, treated with doxycycline at 30 mg/kg) and Group C (high-dose group, doxycycline at 60 mg/kg). The alveolar-arterial oxygen difference (A-aDO2) and respiratory index (RI) were calculated, the concentration of MMP-9 in plasma was measured by ELISA. The expression levels of MMP-9 was determined by RT-PCR. The lung W/D index was calculated. The myeloperoxidase (MPO) activity of bronchoalveolar lavage fluid (BALF) was measured by colorimetry. The total protein of BALF was measured by Coomassie brilliant blue G-250. The white blood count (WBC) in the sediment of BALF was counted. RESULTS A-aDO2, RI, total protein, and MPO activity of BALF, WBC count in BALF sediment and W/D index in group B were significantly lower than that of control group (P < 0.05). The concentration of MMP-9 in group C decreased significantly (P < 0.05). There were no significant differences in gene expression among the three groups. CONCLUSION The results suggested that doxycycline protected the acute lung injury induced by CPB through reducing the concentration of MMP-9 and degradation of the cell membrane, pulmonary neutrophil infiltration and pulmonary edema.