Effects of simvastatin on lung injury induced by ischaemia-reperfusion of the hind limbs in rats

J Int Med Res. 2007 Jul-Aug;35(4):523-33. doi: 10.1177/147323000703500412.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Heme Oxygenase-1 / drug effects
  • Heme Oxygenase-1 / metabolism
  • Hindlimb / blood supply
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Leukocyte Count
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung Diseases / drug therapy*
  • Lung Diseases / metabolism
  • Lung Diseases / pathology
  • Malondialdehyde / metabolism
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Premedication
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Simvastatin / therapeutic use*
  • Up-Regulation / drug effects
  • Water / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Water
  • Malondialdehyde
  • Simvastatin
  • Peroxidase
  • Heme Oxygenase-1