Dexmedetomidine protects liver cell line L-02 from oxygen-glucose deprivation-induced injury by down-regulation of microRNA-711

Y.-X. Zhu, J.-H. Zhou, G.-W. Li, W.-Y. Zhou, S.-S. Ou, X.-Y. Xiao

Department of Anaesthesiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China. xiaoxy224@sina.com

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• Pharmacology

OBJECTIVE: In liver transplantation, long-time portal vein blocking causes the occurrence of ischemic liver injury. Dexmedetomidine, a widely admired anesthetic, has been reported as a protective agent on organs under ischemic condition. The objective of this study was to reveal the role and underlying mechanism of dexmedetomidine in ischemic liver injury.

MATERIALS AND METHODS: L-02 cells were treated with dexmedetomidine during 6 h of oxygen-glucose deprivation (OGD) exposure. The expression of microRNA-711 (miR-711) in cell was overexpressed by miRNA transfection. Then, the following parameters were observed: cell viability, apoptosis, the expression of apoptosis-related proteins, and the expression and the release of Interleukin 1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α).

RESULTS: Apoptosis and inflammation were induced following OGD exposure in L-02 cells, as cell viability was impaired, apoptotic cell rate was increased, caspase-3, and caspase-9 was cleaved, and the expression and release of TNF-α and IL-1β were increased. Dexmedetomidine attenuated OGD-induced apoptosis and inflammation, and dexmedetomidine down-regulated the expression of miR-711. Also, dexmedetomidine blocked the activation of p38 mitogen-activated protein kinase (p38MAPK) and Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signaling upon OGD. Moreover, when miR-711 was overexpressed, dexmedetomidine did not protect L-02 cells against OGD, and did not block p38MAPK and JAK/STAT signaling pathways.

CONCLUSIONS: Dexmedetomidine ameliorated OGD-induced cell apoptosis and inflammation in L-02 cells, exerting protective activities in ischemic liver injury. The anti-OGD effects of dexmedetomidine might be realized by down-regulation of miR-711 and suppression of p38MAPK and JAK/STAT signaling pathways.

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