Yan Gao1, Hong Yin2, Yongfang Zhang2, Yunxia Dong2, Fan Yang2, Xiuying Wu2, Hongtao Liu3. 1. 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. 2. Department of Anesthesiology, Shengjing Hospital, China Medical University Shenyang, 110004, Liaoning, PR China. 3. Department of Anesthesiology, Shengjing Hospital, China Medical University Shenyang, 110004, Liaoning, PR China. Electronic address: liuht1@sj-hospital.org.
Abstract
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-1α/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-1α and p53 expression. After 28 days, Morris water maze (MWM) was performed. RESULTS: 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. CONCLUSION: 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.
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-1α/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-1α and p53 expression. After 28 days, Morris water maze (MWM) was performed. RESULTS: 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/Rbrain injuryrats. CONCLUSION: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.
Authors: Mariana Toricelli; Arthur Antonio Ruiz Pereira; Guilherme Souza Abrao; Helena Nascimento Malerba; Julia Maia; Hudson Sousa Buck; Tania Araujo Viel Journal: Neural Regen Res Date: 2021-01 Impact factor: 5.135