Effects and mechanism of dexmedetomidine on neuronal cell injury induced by hypoxia-ischemia
| Autor: | Duan-Yu Wang, Yong-Jian Yang, Wei-Fu Lei, Ya-Jun Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cell Survival Ischemia Apoptosis Pharmacology medicine.disease_cause Proinflammatory cytokine lcsh:RD78.3-87.3 03 medical and health sciences 0302 clinical medicine Neurotrophic factors medicine Animals Hypnotics and Sedatives Viability assay Rats Wistar Cells Cultured Neurons Notch/NF-κB pathway Kinase business.industry PC12 cells medicine.disease Cell Hypoxia Rats Oxygen carbohydrates (lipids) 030104 developmental biology Anesthesiology and Pain Medicine Glucose Animals Newborn nervous system Cytoprotection Oxidative stress lcsh:Anesthesiology Anesthesia Signal transduction business 030217 neurology & neurosurgery Dexmedetomidine Research Article |
| Zdroj: | BMC Anesthesiology, Vol 17, Iss 1, Pp 1-10 (2017) BMC Anesthesiology |
| ISSN: | 1471-2253 |
| Popis: | Background The present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells. Methods PC12 cells exposed to OGD was used to establish ischemia model. The OGD-induced cell injury was evaluated by alterations of cell viability, apoptosis and expressions of apoptosis-associated proteins. Oxidative stress and expressions of neurotrophic factors after OGD and DMED treatments were also explored. The activation of possible involved signaling pathways were studied after OGD and DMED treatments, along with the addition of inhibitors of these pathways. Finally, the effects of DMED on primary neuronal cells were verified according to the alterations of inflammatory cytokines release and oxidative stress. Results DMED obviously increased cell viability and reduced cell apoptosis as well as ratio of Bax/Bcl-2 in OGD-treated PC12 cells. Then, the OGD-induced changes of LDH, MDA, SOD and GSH-Px as well as decreases of neurotrophic factors were all ameliorated by DMED treatment. Key kinases in Notch/NF-κB signaling pathway were up-regulated by OGD, whereas the up-regulations were decreased by DMED. In addition, inhibitor of Notch or NF-κB could augment the effects of DMED on OGD-induced cell injury. Finally, the protective effects of DMED were verified in primary neuronal cells. Conclusion DMED had protective effect on OGD-induced PC12 cell injury, depending on its anti-apoptotic, anti-oxidative activity and the inhibition of Notch/NF-κB activation. Our findings suggested that DMED could be used as a potential therapeutic drug for cerebral ischemia. |
| Databáze: | OpenAIRE |
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