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Dexmedetomidine protects hippocampal neurons against hypoxia/reoxygenation-induced apoptosis through activation HIF-1α/p53 signaling

Gao, Yan, Yin, Hong, Zhang, Yongfang, Dong, Yunxia, Yang, Fan, Wu, Xiuying, Liu, Hongtao
Life sciences 2019 v.232 pp. 116611
Western blotting, apoptosis, brain damage, caspase-3, cytochrome c, dexmedetomidine, hypoxia, hypoxia-inducible factor 1, immunohistochemistry, memory, mitochondria, models, neurons, rats, signal transduction, yohimbine
To 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.Hypoxia/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.50 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.DEX 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.