Abstract

Hepatic ischemia/reperfusion (IR) injury is a critical contraindication of hepatobiliary surgery and results in severe liver damage. It is imperative to identify underlying pathophysiological mechanisms. In the current study, a rat model of liver IR was established to explore the mechanisms of sevoflurane during surgical intervention on IR. The detection of cytokines was performed using ELISA and reverse transcription‑quantitative polymerase chain reaction and western blot assays were used to detect mRNA and protein expression levels, respectively. The target protein of microRNA (miR)‑9‑5p was identified by in vitro luciferase reporter assay. Cell apoptosis was detected by Annexin‑V/propidium iodide and TUNEL staining assays. The results demonstrated that sevoflurane exerted protective effect against liver IR. Sevoflurane administration ameliorated a cytokine storm by decreasing serum levels of interleukin (IL)‑1 and ‑6 and tumor necrosis factor (TNF)‑α, and improved liver function was determined. IR‑induced damage was mediated by an increase in transcription factor p65 expression and activation of the nuclear factor (NF)‑κB signaling pathway, which were suppressed by sevoflurane treatment. In situ analysis predicted that NFKB3, encoding for p65, may be targeted by miR‑9‑5p and the hypothesis was verified by in vitro reporter assays using wild type and mutant sequences of the NFKB3 3'‑untranslated region. Furthermore, pretreatment of hepatic tissue with a miR‑9‑5p mimic inhibited IR‑associated injury as suggested by the decrease in the Suzuki score and decreased serum levels of TNF‑α, IL‑1 and IL‑6. The results indicated that sevoflurane protected the liver from IR injury by increasing miR‑9‑5p expression and miR‑9‑5p may be a potential treatment target in IR.