Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis.

Lei Li, Yanping Zhan, Haimei Xia, Yunkun Wu, Xiongzhi Wu, Shibiao Chen

International immunopharmacology 2023 Jan

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The application of Sevoflurane (Sev) in neurological diseases has been documented. We herein clarified the role of Sev in intracerebral hemorrhage (ICH). Through bioinformatics analysis, ICH-related microRNA (miRNA) was collected with microRNA-133b (miR-133b) chosen for the study subject. Then, the related downstream gene Forkhead box O4 (FOXO4) was identified. For in vivo assays, an ICH mouse model was established by autologous blood injection. For in vitro assays, hippocampal neurons were extracted from mouse brain tissues, and erythrocyte lysates were employed to simulate in vitro hemorrhage. Interaction between miR-133b and FOXO4 as well as between FOXO4 and BCL2 were assayed. We found decreased miR-133b in the brain tissue of ICH mice and erythrocyte lysate-treated hippocampal neurons. Sev treatment attenuated ICH and hippocampal neuronal apoptosis in mice by upregulating miR-133b. miR-133b targeted FOXO4 expression, and inhibition of FOXO4 attenuated hippocampal neuronal apoptosis by increasing BCL2 expression. Sev attenuated ICH in mice by increasing BCL2 expression through regulation of miR-133b-mediated FOXO4 expression. The findings highlighted the protective effect of Sev on ICH mice through the regulation of miR-133b-mediated FOXO4 expression. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Lei Li, Yanping Zhan, Haimei Xia, Yunkun Wu, Xiongzhi Wu, Shibiao Chen. Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis. International immunopharmacology. 2023 Jan;114:109453