simvastatin attenuates ventilator-induced lung injury in mice辛伐他汀变弱ventilator-induced在小鼠肺损伤.pdf

Müller et al. Critical Care 2010, 14:R143 /content/14/4/R143 RESEARCH Open Access Simvastatin attenuates ventilator-induced lung injury in mice 1* 1 1 2 3 1 Holger C Müller , Katharina Hellwig , Simone Rosseau , Thomas Tschernig , Andreas Schmiedl , Birgitt Gutbier , 1,4 1 5 6 1 1 Bernd Schmeck , Stefan Hippenstiel , Harm Peters , Lars Morawietz , Norbert Suttorp , Martin Witzenrath Abstract Introduction: Mechanical ventilation (MV) is a life saving intervention in acute respiratory failure without alternative. However, particularly in pre-injured lungs, even protective ventilation strategies may evoke ventilator- induced lung injury (VILI), which is characterized by pulmonary inflammation and vascular leakage. Adjuvant pharmacologic strategies in addition to lung protective ventilation to attenuate VILI are lacking. Simvastatin exhibited anti-inflammatory and endothelial barrier stabilizing properties in vitro and in vivo. Methods: Mice were ventilated (12 ml/kg; six hours) and subjected to simvastatin (20 mg/kg) or sham treatment. Pulmonary microvascular leakage, oxygenation, pulmonary and systemic neutrophil and monocyte counts and cytokine release in lung and blood plasma were assessed. Further, lung tissue was analyzed by electron microscopy. Results: Mechanical ventilation induced VILI, displayed by increased pulmonary microvascular leakage and endothelial injury, pulmonary recruitment of neutrophils and Gr-1high monocytes, and by liberation of inflammatory cytokines in the lungs. Further, VILI associated systemic inflammation characterized by blo