• Yan Gao, Hong Yin, Yongfang Zhang, Yunxia Dong, Fan Yang, Xiuying Wu, and Hongtao Liu.
• Department of Anesthesiology, Shengjing Hospital, China Medical University Shenyang, 110004, Liaoning, PR China; Department of Anesthesiology, The First Affiliated Hospital of Hebei North University Hebei, Zhangjiakou 075000, PR China.
• Life Sci. 2019 Sep 1; 232: 116611.

PurposeTo observe the effect of dexmedetomidine (DEX) on mitochondrial apoptosis of hippocampal neurons in hypoxia/reoxygenation (H/R) brain injury in developing rats, and to investigate its regulatory mechanism on HIF-1α/p53 signaling pathway.MethodsHypoxia/reoxygenation model was used in this study. TUNEL assay was performed to detect cell apoptosis. Immunohistochemical analysis and Western-blotting analysis were conducted to detect Cytochrome-C (Cyt-c), APAF-1, Caspase-3, Neuroglobin (Ngb), HIF-1α and p53 expression. After 28 days, Morris water maze (MWM) was performed.Results50 μg/kg DEX improved H/R-induced brain injury and inhibited mitochondrial apoptosis in rats. Western-blotting and Immunohistochemical results demonstrated that DEX could up-regulate Ngb through α2 receptor to inhibit H/R-induced mitochondrial apoptosis. In addition, by adding inhibitors yohimbine and 2-methoxyestradiol (2ME2), we found that DEX could activate HIF-1α/p53 signaling pathway. MWM test showed that DEX could enhance long-term learning and memory of H/R brain injury rats.ConclusionDEX alleviates H/R-induced brain injury and mitochondrial apoptosis in developing rats through α2 receptor, which may be related to activation of HIF-1α/p53 signaling pathway to up-regulate the expression of Ngb.Copyright © 2019 Elsevier Inc. All rights reserved.

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