title: Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice.
abstract: BACKGROUND
  Mechanical ventilation has been documented to paradoxically cause lung injury. As a commonly used volatile anesthetic, sevoflurane has been proven to possess antiinflammatory and antioxidative properties. This study aims to investigate the protective effects of sevoflurane on inflammation and ventilator-induced lung injury during mechanical ventilation in healthy mice.
  
  
  METHODS
  The adult healthy mice were divided into four groups, each consisting of ten subjects: mice in group Con-L(VT) and group Sev-L(VT) were ventilated with tidal volumes of 8 mL/kg for 4 hours, while those in group Con-H(VT) and group Sev-H(VT) were ventilated with tidal volumes of 16 mL/kg instead. Control mice (group Con-L(VT) and Con-H(VT)) were subjected to fresh air, while sevoflurane-treated mice (groups Sev- L(VT) and Sev-H(VT)) were subjected to air mixed with 1 vol% sevoflurane. After 4 hours of ventilation, the bronchoalveolar lavage (BAL) fluid was collected and analyzed for the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10. Lung homogenates were harvested to detect the expression of nuclear factor-kappa B (NF-κB) and heme oxygenase (HO)-1 mRNA by reverse transcription-polymerase chain reaction method. Lung damage was evaluated using the modified Ventilator-Induced Lung Injury histological scoring system.
  
  
  RESULTS
  Compared to group Con-L(VT), the levels of TNF-α, IL-1β, IL-6, and IL-10 in BAL fluid, mRNA expressions of NF-κB and HO-1 in lung tissue, and lung injury scores were significantly increased in group Con-H(VT); compared to group Con-H(VT), group Sev-H(VT) BAL samples showed decreased levels of TNF-α, IL-1β, and IL-6; they also showed increased levels of IL-10, the downregulation of NF-κB mRNA, and HO-1 mRNA upregulation; the lung injury scores were significantly lower in group Sev-H(VT) than group Con-H(VT).
  
  
  CONCLUSIONS
  Mechanical ventilation with high tidal volume might lead to lung injury, which could be significantly, but not completely, attenuated by sevoflurane inhalation by inhibiting the NF-κB-mediated proinflammatory cytokine generation and upregulating HO-1 expression.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, People's Republic of China.
authors.forename: Xiang-qing
authors.initials: XQ
authors.lastname: Xiong
authors.forename: Li-na
authors.initials: LN
authors.lastname: Lin
authors.forename: Liang-rong
authors.initials: LR
authors.lastname: Wang
authors.forename: Li-da
authors.initials: LD
authors.lastname: Jin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006439:Hemodynamics; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D000077149:Sevoflurane; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000187:drug effects; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008565:Membrane Proteins; D008738:Methyl Ethers; D012333:RNA, Messenger; D000077149:Sevoflurane; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: inflammation; lung injury; mechanical ventilation; sevoflurane