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

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LI Xu(Department of Intensive Care Unit, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China)
ZHENG Zhen(Department of Intensive Care Unit, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China)
MA Xiao-chun(Department of Intensive Care Unit, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China)
Journal Title:
Chinese Critical Care Medicine
Volume 24, Issue 10, 2012
Key Word:
Acute lung injury; Unfractionated heparin; Matrix metalloproteinase-2; Matrix metalloproteinase-9

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 onzymelinked 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 (μg/L) and MMP-9 (μg/L) in serum of ALI group were increased,and reached the peak at 6 hours (MMP-2:2.86 ± 0.40 vs.1.21 ± 0.24,MMP-9:2.54 ± 0.29 vs.1.15 ±0.34,both P<0.01); they were down-regulated in UFH group at 6 hours (MMP-2:1.92 ± 0.31 vs.2.86 ± 0.40,MMP-9:1.82 ± 0.26 vs.2.54 ± 0.29,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-2mRNA: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.

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