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Dexmedetomidine protects hippocampal neurons against hypoxia/reoxygenation-induced apoptosis through activation HIF-1α/p53 signaling.
- Source :
-
Life Sciences . Sep2019, Vol. 232, pN.PAG-N.PAG. 1p. - Publication Year :
- 2019
-
Abstract
- 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 α 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-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 α 2 receptor, which may be related to activation of HIF-1α/p53 signaling pathway to up-regulate the expression of Ngb. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DEXMEDETOMIDINE
*APOPTOSIS
*NEURONS
*BRAIN injuries
*LONG-term memory
Subjects
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 232
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 138101356
- Full Text :
- https://doi.org/10.1016/j.lfs.2019.116611