Sevoflurane alleviates LPS-induced acute lung injury via the microRNA-27a-3p/TLR4/MyD88/NF-κB signaling pathway

Acute lung injury (ALI) is a critical syndrome that is associated with a high morbidity and mortality in patients. Sevoflurane has a lung protective effect in ALI as it reportedly has anti-inflammatory and apoptotic-regulating activity. However, the mechanism is still not entirely understood. The aim of the present study was to explore the effects of sevoflurane on lipopolysaccharide (LPS)-induced ALI in mice and the possible mechanisms involved. The results revealed that sevoflurane treatment improved LPS-induced lung injury, as evidenced by the reduction in mortality, lung permeability, lung wet/dry ratio and lung histopathological changes in mice. Total cell counts and the production of pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β and IL-6] in bronchoalveolar fluid were also decreased following treatment with sevoflurane. Additionally, LPS-triggered apoptosis in lung tissues, which was eliminated by sevoflurane. Furthermore, a miRCURY™ LNA array was employed to screen for differentially expressed microRNAs (miRs/miRNAs). Among these miRNAs, 6 were differentially expressed and were involved in the inflammatory response, but only miR-27a-3p (miR-27a) was regulated by sevoflurane. Subsequently, the present study investigated whether sevoflurane exerts its function through the modulation of miR-27a. The results demonstrated that the overexpression of miR-27a via an injection with agomiR-27a produced similar protections as sevoflurane, while the inhibition of miR-27a suppressed the lung protective effects of sevoflurane in ALI mice. In addition, the present study identified that miR-27a inhibited Toll-like receptor 4 (TLR4) by binding to its 3′-untranslated region. Western blot analysis demonstrated that sevoflurane may ameliorate the inflammatory response by blocking the miR-27a/TLR4/MyD88/NF-κB signaling pathway. The present results indicate that sevoflurane may be a viable therapeutic option in the treatment of patients with ALI.