title: Protective effects of hemin in an experimental model of ventilator-induced lung injury.
abstract: Mechanical ventilation is an indispensable life-support modality for critically ill patients with acute lung injury or acute respiratory distress syndrome. Unfortunately, mechanical ventilation even the protective ventilation strategies may evoke ventilator-induced lung injury. Heme oxygenase-1 (HO-1) has recently exhibited anti-inflammatory and anti-oxidative properties in vitro and in vivo. The effect of HO-1 in ventilator-induced lung injury has not been fully characterized. In this study, rabbits were subjected to high tidal volume ventilation to induce ventilator-induced lung injury, which was confirmed by histopathological alterations, increased bronchoalveolar lavage fluid protein content and lung wet-to-dry ratio. In contrast to the level of HO-1 expression in high tidal volume group, pretreatment with hemin, an inducer of HO-1, further up-regulated HO-1 expression. At the same time, these lung injury indexes were attenuated markedly. This pulmonary protection was accompanied by a decrease in bronchoalveolar lavage fluid neutrophil count and in lung myeloperoxidase activity. Besides, pretreatment with hemin prohibited the production of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-8, and up-regulated the level of anti-inflammatory cytokine interleukin (IL)-10 in bronchoalveolar lavage fluid. Furthermore, a decreased malondialdehyde activity, a marker of oxidative stress and a robust increase in total antioxidant capacity were observed in hemin-treated animals. Our findings suggest that HO-1 up-regulation by hemin plays a protective role in ventilator-induced lung injury by suppression inflammatory process and oxidative stress.
authors.affiliation: Department of Pulmonary Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: An
authors.forename: Chang-Ting
authors.initials: CT
authors.lastname: Liu
authors.forename: Xue-Bing
authors.initials: XB
authors.lastname: Qin
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Sen-Yang
authors.initials: SY
authors.lastname: Yu
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015854:Up-Regulation / Q000187:drug effects; D055397:Ventilator-Induced Lung Injury / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D006427:Hemin; D051547:Heme Oxygenase-1