Dexmedetomidine Protects Human Renal Tubular Epithelial Hk-2 Cells Against Hypoxia/Reoxygenation Injury By Inactivating Endoplasmic Reticulum Stress Pathway

Objective: the study was aimed to investigate the effects and potential mechanisms of dexmedetomidine (dex) on hypoxia/reoxygenation (h/r) injury in human renal tubular epithelial hk-2 cells. materials and methods: in this experimental study, hk-2 cells were divided into four groups: control group, dex group, h/r group, and dex+h/r group. the cells in control group received no treatment, and cells in dex group were only treated with 0.1 nmol/l dex. the cells in h/r group and dex+h/r group were all treated with h/r (hypoxia for 24 hours and normoxia for 4 hours), and only the cells in dex+h/r group were pre-administrated with 0.1 nmol/l dex. following treatments at 37˚c for 28 hours, cell viability and apoptosis were measured by mtt assay and flow cytometry, respectively. also, the expressions of hypoxia-inducible factor 1 (hif-1α), glucose-regulated protein 78 (grp78), c/ebp homologous protein (chop), caspase-12 and cleaved caspase-3 were determined by western blot. results: the cell viability was significant decreased in h/r group compared with control group (p<0.05), while was significantly increased in dex+h/r group compared with that in h/r group (p<0.05). however, the change tendency of the cell apoptosis was opposite to that of cell viability. compared with h/r group, the expression of hif-1α was evidently up-regulated, while grp78, chop, capase-12 and cleaved caspase-3 expressions were all obviously downregulated in dex+h/r group (p<0.05). in addition, the concentrations of malondialdehyde (mda) in h/r group and dex+h/r group were 1.68 ± 0.22 nmol/mgprot and 0.85 ± 0.16 nmol/mgprot, respectively. the superoxide dismutase (sod) activity was higher in dex+h/r group (121 ± 11 u/l), which which was more than twice larger than that in h/r group (57 ± 10 u/l). conclusion: dex could promote cell viability and inhibit apoptosis through up-regulating hif-1α, reducing endoplasmic reticulum (er) stress and mediating oxidative stress, thus ameliorating the h/r injury.