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.