Propofol ameliorates ischemia/reperfusion induced cerebral injury by upregulation of microRNA-206 expression

Aims: The aim of this study is to investigate the role of miR-206 in propofol induced protective effects in cerebral ischemia/reperfusion injury and to explore its possible mechanism. Methods: Hypoxia/reoxygenation (H/R) model of mouse motoneuron-like cell line NSC-43 was established, and the expression miR-206 upon propofol treatment was analyzed by Realtime PCR. Cells were transfected with miR-206 mimic (miR-206) or scramble control (NC) and subjected to H/R, followed by propofol treatment or not. Cell viability and apoptosis was detected by CCK8 assay, flow cytometry and Western blot analysis of apoptosis-related proteins. Target of miR-206 was predicted by bioinformatics analysis and verified by Dual-luciferase reporter gene assay and Western blot. An in vivo model of rat cerebral ischemia/reperfusion injury was used to verify the target of miR-206. Before or after propofol treatment, hippocampi were taken for TUNEL assay and Western analysis of Orthodenticle Homeobox 2 (OTX2) expression. Results: Expression of miR-206 was significantly upregulated after propofol treatment in rat hippocampi. MiR-206 transfection significantly increased cell viability and decreased apoptosis rate, which was consistent with the effect of propofol treatment. Both miR-206 transfection and propofol treatment after H/R inhibited the expression of Bax but upregulated Bcl-2 expression. In addition, 3’untranslated region (3’UTR) of OTX2 has a putative binding site for miR-206. MiR-206 could directly bind to the OTX2 3’UTR and negatively regulate the expression of OTX2 protein. Conclusions: Our results indicate that miR-206 was upregulated after propofol treatment in H/R model to decrease the expression of OTX2 protein, reduce the apoptosis of neural cells and finally suppress cerebral ischemia/reperfu-