OBJECTIVE: To investigate effects of dexmedetomidine (DEX) on miR-205-5p/HMGB1 axis in cerebral ischemic/reperfusion (I/R) injury. METHODS: Both in vivo I/R rat model and in vitro hypoxia/reoxygenation (H/R) cell model using rat hippocampal neurons cells were established. miR-205-5p was overexpressed or inhibited by transfection of miR-205-5p mimics or inhibitor. HMGB1 was overexpressed by transfection overexpression plasmids (OE-HMGB1). TTC staining was used for measurement of infraction volume. Oxidative stress was evaluated by measurement of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and inflammation was evaluated by measurement of IL-1β, IL-6 and TNF-α. Dual luciferase reporter assay was performed to confirm binding between miR-205-5p and HMGB1. The expression levels of miR-205-5p, and HMGB1 were measured using RT-qPCR. Western blotting was used to test the protein expression levels of HMGB1, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase 1 (HO-1) and catalase (CAT). RESULTS: Treatment of DEX significantly reduced brain infraction volume, decreased Longa's neurological function score and inhibited oxidative stress and inflammation in brain tissues of I/R rats, which were all reversed by inhibition of miR-205-5p. Both treatment of DEX or overexpression of miR-205-5p restricted oxidative stress and inflammation in H/R rat hippocampal neurons cells. The inhibition of miR-205-5p reversed the effects of DEX, while the overexpression of HMGB1 reversed the effects of miR-205-5p overexpression in H/R rat hippocampal neurons cells. Dual luciferase reporter assay showed miR-205-5p directly targeted HMGB1. CONCLUSION: DEX improved I/R injury by suppressing brain oxidative stress and inflammation DEX improved I/R injury by suppressing brain oxidative stress and inflammation through activating miR-205-5p/HMGB1 axis through activating miR-205-5p/HMGB1 axis.
OBJECTIVE: To investigate effects of dexmedetomidine (DEX) on miR-205-5p/HMGB1 axis in cerebral ischemic/reperfusion (I/R) injury. METHODS: Both in vivo I/R rat model and in vitro hypoxia/reoxygenation (H/R) cell model using rat hippocampal neurons cells were established. miR-205-5p was overexpressed or inhibited by transfection of miR-205-5p mimics or inhibitor. HMGB1 was overexpressed by transfection overexpression plasmids (OE-HMGB1). TTC staining was used for measurement of infraction volume. Oxidative stress was evaluated by measurement of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and inflammation was evaluated by measurement of IL-1β, IL-6 and TNF-α. Dual luciferase reporter assay was performed to confirm binding between miR-205-5p and HMGB1. The expression levels of miR-205-5p, and HMGB1 were measured using RT-qPCR. Western blotting was used to test the protein expression levels of HMGB1, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase (GPx), glutathione reductase (GR), heme oxygenase 1 (HO-1) and catalase (CAT). RESULTS: Treatment of DEX significantly reduced brain infraction volume, decreased Longa's neurological function score and inhibited oxidative stress and inflammation in brain tissues of I/R rats, which were all reversed by inhibition of miR-205-5p. Both treatment of DEX or overexpression of miR-205-5p restricted oxidative stress and inflammation in H/R rat hippocampal neurons cells. The inhibition of miR-205-5p reversed the effects of DEX, while the overexpression of HMGB1 reversed the effects of miR-205-5p overexpression in H/R rat hippocampal neurons cells. Dual luciferase reporter assay showed miR-205-5p directly targeted HMGB1. CONCLUSION: DEX improved I/R injury by suppressing brain oxidative stress and inflammation DEX improved I/R injury by suppressing brain oxidative stress and inflammation through activating miR-205-5p/HMGB1 axis through activating miR-205-5p/HMGB1 axis.