Effect of remimazolam on OGD/R-induced autophagy and apoptosis in neural cells by regulating the HIF-1α/BNIP3 signaling pathway
Objective To explore the effect and underlying mechanism of remimazolam on oxygen glucose deprivation/reoxygenation(OGD/R)-induced neuronal ischemia-reperfusion injuries of autophagy and apoptosis.Methods The mouse hippocampal neuron cell line HT22 was cultured in vitro,and subjected to OGD/R.The concentration of remimazolam used in this experiment was screened.HT22 cells were induced with blank control,OGD/R,remimazolam,2-ME2 and 2-ME2+remimazolam.Cell viability,apoptosis,autophagosomes were detected by CCK-8 assay,flow cytometry and transmission electron microscopy(TEM),respectively.Protein expressions of hypoxia inducible factor-1(HIF-1α),BCL2 interacting protein 3(BNIP3)and light chain 3(LC3)-Ⅱ(LC3-Ⅱ)/LC3-Ⅰ were detected by Western blot.Results The concentration of remimazolam used in this experiment was determined to be 50μg/ml.Compared with those of blank control,OGD/R-induced HT22 cells presented with significantly lower OD450 and protein expressions of HIF-1α,BNIP3 and LC3-Ⅱ/LC3-Ⅰ,but significantly higher apoptotic rate(P＜0.05).Compared with those induced with OGD/R,HT22 cells induced with remimazolam presented with significantly higher number of autophagosomes,OD450 and protein expressions of HIF-1α,BNIP3 and LC3-Ⅱ/LC3-Ⅰ,but significantly lower apoptotic rate(P＜0.05).Compared with those induced with OGD/R,HT22 cells induced with 2-ME2 presented with significantly lower number of autophagosomes,OD450 and protein expressions of HIF-1α,BNIP3 and LC3-Ⅱ/LC3-Ⅰ,but significantly higher apoptotic rate(P＜0.05).Compared with those induced with remimazolam,HT22 cells induced with remimazolam+2-ME presented with significantly lower number of autophagosomes,OD450 and protein expressions of HIF-1α,BNIP3 and LC3-Ⅱ/LC3-Ⅰ but significantly higher apoptotic rate(P＜0.05).Compared with those induced with 2-ME,HT22 cells induced with remimazolam+2-ME presented with significantly higher number of autophagosomes,OD450 and protein expressions of HIF-1α,BNIP3 and LC3-Ⅱ/LC3-Ⅰ,but significantly lower apoptotic rate(P＜0.05).Conclusion Remimazolam can promote OGD/R-induced autophagy and inhibit apoptosis of neural cells by activating the HIF-1α/BNIP3 signaling pathway,thereby alleviating OGD/R-induced neuronal damage.
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万方数据
维普
