Role of microRNA-218-5p in sevoflurane-induced protective effects in hepatic ischemia/reperfusion injury mice by regulating GAB2/PI3K/AKT pathway

Hepatic ischemia/reperfusion (I/R) injury (HIRI) often occurs following tissue resection, hemorrhagic shock or transplantation surgery. Previous investigations showed that sevoflurane (Sevo), an inhalation anesthetic, had protective properties against different organ damage in animal models including HIRI. This study is aimed to investigate the underlying mechanisms involved in the protective effects of Sevo on HIRI. The present study results showed that treatment with Sevo improved histologic damage, inflammatory response, oxidative stress and apoptosis after hepatic I/R, indicating the protective role of Sevo against liver I/R injury. Importantly, in order to determine the molecular mechanism of Sevo in HIRI, the focus of the study was on microRNA (miR) regulation. By retrieving the microarray data in the Gene Expression Omnibus dataset (GSE72315), miR-218-5p was found to be significantly downregulated by Sevo. Moreover, miR-218-5p overexpression using agomiR-218-5p reversed the protective roles of Sevo against HIRI. Furthermore, GAB2, a positive regulator of PI3K/AKT signaling pathway, was found as a target gene of miR-218-5p. It was also found that the Sevo-mediated protective effects may be dependent on the activation of GAB2/PI3K/AKT. Collectively, these data revealed that Sevo alleviated HIRI in mice by restraining apoptosis, relieving oxidative stress and inflammatory response through the miR-218-5p/GAB2/PI3K/AKT pathway, which helps in understanding the novel mechanism of the hepatic-protection of Sevo.