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

Wang,Yunfei; Zhang,Xiaoran; Tian,Jianmin; Liu,Guoze; Li,Xiaofang; Shen,Dan

doi:10.3892/ijmm.2019.4217

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

Authors:
- Yunfei Wang
- Xiaoran Zhang
- Jianmin Tian
- Guoze Liu
- Xiaofang Li
- Dan Shen
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: May 30, 2019 https://doi.org/10.3892/ijmm.2019.4217
Pages: 479-490
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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