Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

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). CONCLUSION: 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.