Effects of simvastatin on lung injury induced by ischaemia-reperfusion of the hind limbs in rats.
We investigated whether simvastatin reduces lung injury caused by ischaemia-reperfusion of the hind limbs in rats. The control group underwent dissection of bilateral femoral arteries; another group (I/R group) underwent ischaemia of bilateral hind limbs for 2 h followed by 3 h reperfusion; and two other groups were pretreated with 5 or 10 mg/kg per day simvastatin for 3 days and then underwent ischaemia-reperfusion. The control and I/R group rats received placebo (water) instead of simvastatin. The lungs of the I/R rats showed marked histopathological changes compared with the other groups. Lung tissue myeloperoxidase, malondialdehyde, neutrophil count and lung injury scores in both simvastatin groups were significantly lower than in the I/R group; 10 mg/kg per day simvastatin significantly reduced lung water content although 5 mg/kg per day did not. Expression of haem oxygenase-1 (HO-1) protein in lung tissue was significantly greater in the simvastatin groups than in the I/R group. Simvastatin protects against lung injury associated with lower extremity ischaemia-reperfusion by reduction of neutrophil aggregation and oxidative damage, and upregulation of HO-1 expression in the injured lung.
Sun
X F
XF
Department of Anaesthesiology, The First Affiliated Hospital, China Medical University, Shenyang, China.
Wang
L L
LL
Wang
J K
JK
Yang
J
J
Zhao
H
H
Wu
B Y
BY
Wang
Y F
YF
Wang
L
L
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019821:Simvastatin / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects; D014867:Water / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014867:Water; D008315:Malondialdehyde; D019821:Simvastatin; D009195:Peroxidase; D051547:Heme Oxygenase-1