title: Long-term administration of simvastatin reduces ventilator-induced lung injury and upregulates heme oxygenase 1 expression in a rat model.
abstract: BACKGROUND
  Simvastatin reduces ventilator-induced lung injury and is regularly used in clinical practice. This study aimed to test the hypotheses that long-term use of simvastatin could affect the incidence and severity of ventilator-induced lung injury after mechanical ventilation, and the process may involve heme oxygenase-1 (HO-1).
  
  
  METHODS
  Forty healthy adult Sprague-Dawley rats were randomly divided into four groups, namely control, ventilation, simvastatin, and simvastatin + ventilation groups. Saline (control and ventilation groups) or 10 mg kg(-1) d(-1) simvastatin (simvastatin and simvastatin + ventilation groups) was administered by gavage to the animals for 4 wk. Mechanical ventilation (tidal volume 50 mL/kg) was then applied for 4 h to the ventilation and simvastatin + ventilation groups. Lung tissues were harvested for hematoxylin-eosin staining and pathologic examination, and HO-1 contents were measured by immunoblotting and polymerase chain reaction.
  
  
  RESULTS
  A severe pathologic damage was observed in rats that underwent mechanical ventilation. Interestingly, protein concentration, wet/dry weight ratio, myeloperoxidase activity, and malondialdehyde level were increased, and superoxide dismutase activity decreased, in lung tissues after mechanical ventilation. The pathologic damage was substantially alleviated in rats treated with simvastatin before mechanical ventilation: reduced protein concentration, wet/dry weight ratio, myeloperoxidase activity, and malondialdehyde level, and increased superoxide dismutase activity in lung tissues, compared with the ventilation group. Both mechanical ventilation and simvastatin administration induced HO-1 messenger RNA and protein expression in lung tissues.
  
  
  CONCLUSIONS
  Long-term administration of simvastatin significantly reduces the inflammatory response and pulmonary injury induced by mechanical ventilation, potentially by upregulating HO-1 in lung tissues.
authors.affiliation: Department of Critical Care Medicine, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. Electronic address: zhaowenjingccm@126.com.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Xianyang Hospital of Yan'an University, Xianyang, China.
authors.forename: Haigang
authors.initials: H
authors.lastname: Song
authors.affiliation: Faculty of Graduate Studies, Xuzhou Medical College, Xuzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D019821:Simvastatin / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D055397:Ventilator-Induced Lung Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008315:Malondialdehyde; D019821:Simvastatin; D009195:Peroxidase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D013482:Superoxide Dismutase
keywords: Heme oxygenase-1; Mechanical ventilation; Simvastatin