Dexmedetomidine Inhibits The Necroptosis Mediated And Hypoxia-induced Damage And Inflammation In HT22 Cells

Background and ObjectiveHypoxemia refers to the partial pressure of oxygen in arterial blood is not higher than 60 mmHg.Hypoxemia is one of the important factors in the pathophysiological process of stroke,ischemia,and brain edema.Therefore,it is an important issue to study a variety of drugs and their mechanisms can anti-hypoxia.Dexmedetomidine?Dex?,as an alpha-2receptor agonist,has protective effects on hypoxia-induced neurological damage.Previous studies have confirmed that necroptosis?Nec?mediates the damage and inflammation in HT22 cells that induced by chemical hypoxia.Therefore,this study explores whether Dex reverses the damage and inflammation mediated by Nec of HT22 cells which induced by chemical hypoxia.MethodThe cytochemical hypoxia model of HT22 cells was established by cobalt dichloride?CoCl₂?of 600?M for 36 hours.Cell Counting kit-8?CCK-8?was used to detect the survival rate of HT22 hippocampal neurons.Fluorescein-diacetate?DCFHDA?was used to stain fluorescein.The levels of reactive oxygen species?ROS?in cells were measured by light microscopy photography.Mitochondrial membrane potential?MMP?was detected by JC-1 staining flow cytometry.The expression level of receptor-interacting protein 3?RIP3?and tumor necrosis factor alpha?TNF-??were detected by protein immunoblotting.Result1)The activity of HT22 cells decreased significantly,ROS production increased,MMP level decreased,RIP3 and TNF-?expression increased after it was exposed to cobalt dichloride at 600?M for 36 hours.The Necrostatin-1,a necrotizing apoptotic inhibitor of 80?M,could inhibit the decrease of cell activity,reduce the production of ROS,increase the level of MMP,and decrease the expression of RIP3 and TNF-?.2)Decrease of cell activity was inhibited by co-treatment of dexmedetomidine with 10-100?M.After co-treatment with dexmedetomidine with 50?M,ROS production was decreased,MMP level was increased,RIP3 and TNF-?expression was decreased.ConclusionDexmedetomidine has protective effect on the necroptosis mediated and hypoxia-induced damage and inflammation in HT22 cells.