[Effects of unfractionated heparin on expression of metalloproteinase-2 and -9 in acute lung injury rats].

Abstract

Objective: To determine the activation of matrix metalloproteinase (MMP-2, MMP-9) in rats with acute lung injury (ALI) and the effects of unfractionated heparin (UFH) on the levels.

Methods: Eighteen male Wistar rats were divided into control group, ALI group and UFH group, with 6 rats in each group by means of random number table. ALI was induced by administering a bolus injection of lipopolysaccharide (LPS) via the caudal vein at a dose of 6 mg/kg. In UFH group the rats were treated intravenously with 100 U/kg of UFH 15 minutes before the injection of LPS. In control group, the rats were treated with the same volume of normal saline. Serum levels of MMP-2 and MMP-9 were measured by enzyme linked immunosorbent assay (ELISA) at 1, 3, 6 hours via femoral vein. Six hours after the injection of reagents, the rats were sacrificed and lung tissue samples were collected for mRNA analysis of the MMP-2 and MMP-9 by real-time fluorescence quantitate reverse transcription-polymerase chain reaction (qRT-PCR).

Results: Compared with control group, the content of MMP-2 and MMP-9 in serum of ALI group were increased, and reached the peak at 6 hours (MMP-2: 2.86±0.40 μg/L vs. 1.21±0.24 μg/L, MMP-9: 2.54±0.29 μg/L vs. 1.15±0.34 μg/L, both P<0.01); they were down-regulated in UFH group at 6 hours (MMP-2: 1.92±0.31 μg/L vs. 2.86±0.40 μg/L, MMP-9: 1.82±0.26 μg/L vs. 2.54±0.29 μg/L, both P<0.05). Compared with control group, the mRNA expressions of MMP-2 and MMP-9 in the lung tissue of ALI group were increased at 6 hours (MMP-2 mRNA: 1.88±0.09 vs. 1.00±0.10, MMP-9 mRNA: 3.15±0.47 vs. 1.00±0.17, both P<0.01); they were down-regulated in UFH group (MMP-2 mRNA: 1.26±0.14 vs. 1.88±0.09, P<0.01; MMP-9 mRNA: 2.06±0.68 vs. 3.15±0.47, P<0.05), but still above the control group (both P<0.05).

Conclusions: The present study demonstrated that the level of MMP-2 and MMP-9 increased in rats with ALI. UFH could exert protective effects by inhibiting expression of MMP-2 and MMP-9 in serum and lung tissue, in both mRNA and protein expression.