title: Volatile anesthetic sevoflurane ameliorates endotoxin-induced acute lung injury via microRNA modulation in rats.
abstract: Volatile anesthetics have a lung protective effect in acute lung injury (ALI). Our previous study showed sevoflurane affects the expression of microRNA (miRNA) that control various physiological systems by regulating messenger RNA (mRNA) expression. However, the association between the anti-inflammatory effect of sevoflurane and miRNAs modulation remains unknown. The aim of the present study was to investigate the effect of sevoflurane and the expression of miRNAs in an endotoxin-induced ALI model in rats. Wistar rats were randomly assigned to three groups [lipopolysaccharide (LPS), LPS-sevoflurane and control; n=8/group]. All the rats were mechanically ventilated and intravenously-administered LPS (saline as control). Two hours post-injury, general anaesthesia was performed for 4 h with 2% sevoflurane (LPS-sevoflurane). The LPS and the control groups did not receive anaesthesia. The severity of ALI was evaluated by partial pressure of oxygen/fraction of inspired oxygen and the mRNA expression of inflammatory cytokine. The miRNA expression in lung tissue was analyzed by a reverse transcription-quantitative polymerase chain reaction. LPS caused ALI, evidenced by the impairment of pulmonary function and increased mRNA levels of tumor necrosis factor-α, interleukin-6 and nuclear factor-κB. Sevoflurane improved pulmonary function and inhibited the increased mRNAs. Of the 219 miRNAs detected, 15 and nine miRNAs were significantly changed in the LPS and LPS-sevoflurane group, respectively. In the LPS-sevoflurane group, the expression of several miRNAs that regulate inflammation was significantly changed compared to the LPS group. In conclusion, the present data showed that sevoflurane influences the expression of the miRNAs that regulate inflammation. This result suggests that the changes in miRNA expression are involved in the lung protective mechanisms of volatile anesthetics.
authors.affiliation: Department of Anaesthesiology and Pain Medicine Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Otsuki
authors.affiliation: Department of Anaesthesiology and Pain Medicine Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Anaesthesiology and Pain Medicine Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Department of Anaesthesiology and Pain Medicine Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Gentaro
authors.initials: G
authors.lastname: Goto
authors.affiliation: Department of Anaesthesiology and Pain Medicine Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sakamoto
keywords: acute lung injury; microRNA; postconditioning; sevoflurane; volatile anaesthetics