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

Purpose: 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-1 alpha/p53 signaling pathway. Methods: 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-1 alpha and p53 expression. After 28 days, Morris water maze (MWM) was performed. Results: 50 mu g/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 alpha(2) 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-1 alpha/p53 signaling pathway. MWM test showed that DEX could enhance long-term learning and memory of H/R brain injury rats. Conclusion: DEX alleviates H/R-induced brain injury and mitochondrial apoptosis in developing rats through alpha(2) receptor, which may be related to activation of HIF-1 alpha/p53 signaling pathway to up-regulate the expression of Ngb.