Role of Sigma-1 receptor in pentazoxine-induced reduction of oxygen-glucose deprivation and restoration injury in SH-SY5Y cells: relationship with endoplasmic reticulum stress / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of Sigma-1 receptor (Sigma-1R) in pentazoxine-induced reduction of oxygen-glucose deprivation and restoration (OGD/R) injury in SH-SY5Y cells and the relationship with endoplasmic reticulum stress (ERS).Methods:The well-growing SH-SY5Y cells were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), OGD/R group (group O), OGD/R+ pentazoxin group (group OP) and OGD/R+ pintazoxin+ BD1047 group (group OPB). The cells in group C were normally cultured. In O group, OP group and OPB group, the culture medium was replaced with EBSS medium, and then the cells were cultured in an incubator of 5% CO 2-95% N 2 at 37 ℃ for 4 h, then replaced with DMEM/F12 medium containing 10% fetal bovine serum for restoration of O 2-glucose supply for 18 h, and in addition pentazoxin (final concentration 10 μmmol/L) was added during restoration in OP group, and pentazoxin (final concentration 10 μmmol/L) and Sigma-1R blocker BD1047 (final concentration 20 μmol/L) were added during restoration in OPB group. The apoptosis rate was detected by flow cytometry at the end of restoration, and the expression of Sigma-1R, C/EBP homologous protein (CHOP), phosphorylated inositol-requiring enzyme 1 (p-IRE1), spliced X-box binding protein 1 (XBP1s), and activated caspase-3 (c-cas-3) was detected by Western blot. Results:Compared with group C, the apoptosis rate was significantly increased, and the expression of CHOP and p-IRE1 was up-regulated in O group, OP group and OPB group, the expression of XBP1s and c-cas-3 was significantly up-regulated in O group and OPB group ( P<0.05), and no significant change was found in the expression of Sigma-1R, XBP1s and c-cas-3 in OP group ( P>0.05). Compared with O group, the apoptosis rate was significantly decreased, the expression of Sigma-1R was up-regulated, and the expression of CHOP, p-IRE1, XBP1s and c-cas-3 was down-regulated in OP group ( P<0.05). Compared with OP group, the apoptosis rate was significantly increased, the expression of Sigma-1R was down-regulated, and the expression of CHOP, p-IRE1, XBP1s and c-cas-3 was up-regulated in OPB group ( P<0.05). Conclusions:Sigma-1R is involved in pentazoxine-induced reduction of OGD/R injury in SH-SY5Y cells, and the mechanism may be related to inhibition of endoplasmic reticulum stress.