Matrix metalloprotease expressions in both reperfusion lung injury and oleic acid lung injury models and the protective effects of ilomastat.
OBJECTIVE
Our aim was to study the expressions of matrix metalloprotease 9 (MMP9) and the effects of the MMP inhibitor Ilomastat in both ischemia/reperfusion (I/R)- and oleic acid (OA)-induced lung injury models.


METHODS
Real-time polymerase chain reactions and Western blots were used to assess mRNA and protein expressions of MMP9 in lung tissues after I/R or OA lung injury. Ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the OA model, lung injury was induced by intravenous infusion of OA (0.1 mL/kg) for 20 minutes and then observation for 6 hours. Lavage leukocyte concentration and wet/dry lung weight ratio were used to assess lung inflammation and injury. Blood samples were collected for assays of hydroxyl radicals and nitric oxide. The MMP inhibitor Ilomastat (100 microg/kg) was administered before I/R and OA infusion.


RESULTS
mRNA and protein expressions of MMP9 were significantly increased in both lung injury models. Ilomastat decreased MMP9 mRNA and protein expressions but did not reach statistical significance. Blood concentrations of hydroxyl radicals and nitric oxide, wet/dry lung weight ratios, and lavage leukocyte concentrations were significantly higher in both experimental groups compared with the sham group (P < .001). Ilomastat significantly attenuated the extent of lung inflammation and injury induced by both I/R and OA.


CONCLUSIONS
MMP may play a critical role in the lung injury induced by I/R and OA infusion.
Yeh
D Y
DY
Division of Chest Medicine, Department of Internal Medicine, Shin Kong Wu-Ho-Su Memorial Hospital, Taipei, Taiwan.
Lin
H I
HI
Feng
N H
NH
Chen
C F
CF
Wang
D
D
Wang
N T
NT
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005268:Femoral Vein / Q000187:drug effects / Q000502:physiology; D006877:Hydroxamic Acids; D017665:Hydroxyl Radical / Q000378:metabolism; D007211:Indoles / Q000627:therapeutic use*; D007958:Leukocyte Count; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D055370:Lung Injury / Q000517:prevention & control*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D061965:Matrix Metalloproteinase Inhibitors; D019301:Oleic Acid / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019301:Oleic Acid; D017665:Hydroxyl Radical; D020780:Matrix Metalloproteinase 9; C119203:ilomastat