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.
IntroductionAcute lung injury (ALI) is a major complication in critically ill patients (1). Therefore, it is important to preserve lung function and prevent further exacerbation for those patients whose lungs are already vulnerable prior to surgery. The volatile anesthetic sevoflurane is known to have organ protective effects in several pathological conditions. For example, Voigtsberger et al (2) have recently shown that sevoflurane ameliorates gas exchange and attenuates lung damage in a model of lipopolysaccharide (LPS)-induced ALI.MicroRNA (miRNA) is a newly discovered and non-coding RNA that regulates genome expression at the post-transcriptional level (3). miRNA is estimated to control 30-90% of human genes (4). miRNA has been suggested to either suppress messenger RNA (mRNA) translation or reduce mRNA stability by binding particular regions of mRNA (5). Recent published data have also revealed that the expression and function of miRNA are associated with a broad range of diseases.In our previous study, it was found that sevoflurane affects the expression of miRNAs in normal rat lung (6). However, such effects of anesthetic ALI ...