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目的研究孤儿核受体NR2E1对棕榈酸(PA)诱导的胰岛β细胞凋亡及内质网应激的影响。方法建立过表达NR2E1小鼠胰岛细胞系NIT1细胞株,予500μmol/L PA处理24 h,采用流式细胞仪检测细胞凋亡,RT-PCR检测C/EBP同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)mRNA表达变化,Western blot检测磷酸化真核翻译起始因子2α(p-eIF2α)的水平。结果过表达NR2E1能减少PA诱导的NIT1细胞凋亡率[(27.5±0.4)%vs(11.9±0.4)%]和CHOP mRNA表达[(10.54±1.98)vs(3.03±0.49)],增加GRP78 mRNA表达[(3.28±0.20)vs(5.28±0.49)]和eIF2α磷酸化水平[(1.26±0.13)vs(1.67±0.06)](P<0.05)。结论过表达NR2E1能减轻PA诱导的胰岛β细胞凋亡,其机制可能与调节内质网应激有关。
Objective To study the effects of orphan nuclear receptor NR2E1 on the islet β cell apoptosis and endoplasmic reticulum stress induced by palmitic acid (PA). Methods NIT1 cells were overexpressed in mouse pancreatic islet cell line NR2E1 and treated with 500μmol / L PA for 24 hours. Cell apoptosis was detected by flow cytometry. The levels of C / EBP homologue protein (CHOP), glucose regulatory protein 78 (GRP78) mRNA expression was detected by Western blot detection of phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) levels. Results Overexpression of NR2E1 decreased the apoptosis rate of NIT1 cells induced by PA [(27.5 ± 0.4)% vs (11.9 ± 0.4)%] and CHOP mRNA expression (10.54 ± 1.98 vs 3.03 ± 0.49) (3.28 ± 0.20 vs 5.28 ± 0.49) and eIF2α phosphorylation (1.26 ± 0.13 vs 1.67 ± 0.06, P <0.05). Conclusion Overexpression of NR2E1 can attenuate PA-induced pancreatic β-cell apoptosis, which may be related to the regulation of endoplasmic reticulum stress.