Objective To investigate the neuroprotective effects of dexmedetomidine(Dex)against oxygen-glucose depriva-tion/reoxygenation(OGD/R)injury of cortical neurons and its possible mechanism of action.Methods The cortical neurons of fetal Sprague-Dawley rats(gestational age,18 d)were cultured and then were randomly divided into sham group(cultured in a sugar-containing medium in normal incubator),OGD/R group(cultured in a sugar-free medium in an anaerobic incubator at 37 ℃to prepare a neuronal OGD/R injury model),OGD/R+LW6 group(OGD/R neurons treated with 1 mmol/L LW6 for 1 h as a po-sitive control),OGD/R+low-concentration Dex group(OGD/R neurons treated with 0.1 μmol/L Dex for 1 h),and OGD/R+high-concentration Dex group(OGD/R neurons treated with 1.0 μmol/L Dex for 1 h).The survival rate of cells was determined by co-lorimetric assay with Cell Counting Kit-8(CCK-8)and immunofluorescence assay.The expression levels of hypoxia-inducible factor-1α(HIF-1α),activating transcription factor 6(ATF-6),and the downstream target C/EBP homologous protein(CHOP)were mea-sured by Western blot.Results According to CCK-8 and immunofluorescence assay results,there was a significant diffe-rence in the survival rate of neurons between the groups(F=63.46,P＜0.05).Pairwise comparison showed that the survival rate in the OGD/R group was significantly lower than that in the sham group(P＜0.05);and the survival rate of the OGD/R+high-con-centration Dex group was significantly increased compared with that of the OGD/R group(P＜0.05).Western blot results showed significant differences in the expression of HIF-1α,ATF-6,and CHOP proteins(F=80.30-155.36,P＜0.05).Pairwise compari-son showed that the expression of HIF-1α,ATF-6,and CHOP was significantly higher in the OGD/R group than in the sham group(P＜0.05);and the OGD/R+high-concentration Dex group showed significantly lower expression of HIF-1α,ATF-6,and CHOP compared with the OGD/R group,the differences are statistically significant(P＜0.05).Conclusion Dex inhibits HIF-1α expression to exert protective effects in the neuronal model of OGD/R injury.
维普
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