Dexmedetomidine Suppresses Glutamate-Stimulated Neuronal Injury Via MicroRNA-433/Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Pathway

Background: Cerebral ischemia has been a hotpot in the prevention and treatment of cerebral ischemia. Dexmedetomidine (Dex) is a new type of highly selective α2 adrenergic receptor agonist with pharmacological properties.Objective: Quantitative studies have shown that Dex has a protective effect on glutamate (Glu)-induced neuronaldamage. however, its mechanism has not been fully elucidated. The purpose of this study was to explore the underlyingmolecular mechanism by which Dex ameliorates Glu-induced neuronal injury by regulating miR-433/JAK2/STAT3axis.Materials and Methods: A model of neuronal injury was constructed by Glu treatment and intervened with Dex.miRNA expression profiling assay was conducted to screen potential miRNAs affected by Dex. Cell viability, lactatedehydrogenase (LDH) release and apoptosis were detected by MTT assay, LDH kit, and TUNEL staining, respectively.Oxidative stress indicators were assessed by ELISA whereas mitochondrial membrane potential (MMP) was assessedby C11-BODIPY581/591 staining. The targeting relationship between the miR-433 and JAK2 was verified by dualluciferase reporter assay and gene expression was analyzed by quantitative PCR and Western blot.Results: Glu treatment decreased cell viability and MMP and promoted LDH release, apoptosis and oxidative damage.Glu-induced changes in neurons were reversed after Dex treatment through upregulating the miR-433 expression toblock the activation of JAK2/STAT3 pathway.Conclusions: Dex protects against Glu-induced neuronal injury by regulating miR-433/JAK2/STAT3 pathway, whichprovides new insights into the treatment of neuronal injury.