Effects of matrix metalloproteinase inhibitor on ventilator-induced lung injury in rats

Je Hyeong Kim, Soo Yeon Park, Gyu Young Hur, Seung Heon Lee, Sang Yeub Lee, Sang Myeon Park, In Bum Suh, Chol Shin, Jae Jeong Shim, Kwang Ho In, Kyung Ho Kang, Se Hwa Yoo

Research output: Contribution to journalArticle

Abstract

Background: Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and ARDS patients. Cyclic mechanical stress also can induce MMP-9 production from alveolar macrophages and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods: Eighteen Sprague-Dawley rats were divided into three groups: low tidal volume (LVT, 7mL/Kg tidal volume, 3 cmH2O PEEP, 40/min.), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 IgG1. Results: In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was 4.70±0.14, 6.82±1.28 and 4.92±0.98, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was 3.25±1.17, 12.83±1.17 and 4.67±0.52, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was 3.33±2.07, 12.17±2.79 and 3.60±1.95, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion: VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

Original languageEnglish
Pages (from-to)619-634
Number of pages16
JournalTuberculosis and Respiratory Diseases
Volume53
Issue number6
Publication statusPublished - 2002 Dec 1

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Keywords

  • Acute lung injury
  • Matrix metalloproteinase
  • Matrix metalloproteinase inhibitor
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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