The protection of dexmedetomidine against chemical hypoxia-induced neurons injury and its mechanism

Objective To investigate whether α2-adrenoreceptor agonist dexmedetomidine(Dex) protects PC12 cells against chemical hypoxia-induced injury by inhibiting p38MAPK pathway.Methods PC12 cells were treated with cobalt chloride(CoCl2) to establish a model of chemical hypoxia-induced neuronal injury.Expression of p38 mitogen-activated protein kinase(MAPK) protein was measured by Western blot assay.Cell viability was assessed by cell counter kit(CCK-8).The changes in morphology and the apoptotic cell count were observed by Hoechst 33258 staining.Mitochondrial membrane potential(MMP) was measured by rhodamine123 staining and photofluorography.Results Exposure of PC12 cells to 600 μmol/L CoCl2 significantly enhanced the expression of phosphorylated(p) p38MAPK at the duration between 60 and 180 min,peaking at 120 min.Dex at 400 μmol/L not only protected PC12 cells against CoCl2-induced cytotoxicity,apoptotic effect and MMP damage,but also inhibited up-regulation of p-p38MAPK induced by CoCl2.SB203580,an inhibitor of p38MAPK,mimicked the neuroprotective effect of Dex against chemical hypoxia-induced injury,evidenced by increases in both cell viability and MMP,as well as decrease in apoptotic cells.Conclusion Dex can protect neuronal cells against chemical hypoxia-induced injury,inhibition of p38MAPK pathway may be one of the mechanisms responsible for this effect.