Identification of miRNAs Involved in the Protective Effect of Sevoflurane Preconditioning Against Hypoxic Injury in PC12 Cells

The mechanism of sevoflurane preconditioning-induced neuroprotection is poorly understood. This study was aimed at identifying microRNAs (miRNAs) involved in the protective effect of sevoflurane preconditioning against hypoxic injury using the miRCURYTM LNA Array. The screened differentially expressed miRNAs were further validated using qRT-PCR. Finally, after transfection of miRNA (miR-101a or miR-34b) mimics or inhibitor, MTT and flow cytometry assays were used to evaluate cell survival and apoptosis in sevoflurane preconditioning. qRT-PCR confirmed the changes in expression of differentially expressed miRNAs that were screened by the microarray: down-regulation of rno-miR-101a, rno-miR-106b, and rno-miR-294 and up-regulation of rno-miR-883, rno-miR-16, and rno-miR-34b. MiR-101a and miR-34b were the most differentially expressed miRNAs. Sevoflurane preconditioning-inhibited apoptosis and preconditioning-enhanced cell viability of PC12 cells were significantly attenuated by transfection of miR-101a mimetic or miR-34b inhibitors, but were significantly enhanced by transfection of miR-34b mimetic. Therefore, a number of miRNAs, including miR-101a and miR-34b, might play important roles in the neuroprotection induced by sevoflurane preconditioning. Such miRNAs might provide novel targets for preventive and therapeutic strategies against cerebral ischemia–reperfusion injury.