中国当代儿科杂志2016,Vol.18Issue(9):867-873,7.DOI:10.7499/j.issn.1008-8830.2016.09.016
需肌醇酶1介导的内质网应激通路参与高氧所致早产大鼠肺泡Ⅱ型上皮细胞凋亡
Association between endoplasmic reticulum stress pathway mediated by inositol-requiring kinase 1 and AECII apoptosis in preterm rats induced by hyperoxia
摘要
Abstract
ObjectiveTo study the association between endoplasmic reticulum stress (ERS) pathway mediated by inositol-requiring kinase 1 (IRE1) and the apoptosis of type II alveolar epithelial cells (AECIIs) exposed to hyperoxia. MethodsThe primarily cultured AECIIs from preterm rats were devided into an air group and a hyperoxia group. The model of hyperoxia-induced cell injury was established. The cells were harvested at 24, 48, and 72 hours after hyperoxia exposure. An inverted phase-contrast microscope was used to observe morphological changes of the cells. Annexin V/PI double staining lfow cytometry was performed to measure cell apoptosis. RT-PCR and Western blot were used to measure the mRNA and protein expression of glucose-regulated protein 78 (GRP78), IRE1, X-box binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP). An immunofluorescence assay was performed to measure the expression of CHOP.ResultsOver the time of hyperoxia exposure, the hyperoxia group showed irregular spreading and vacuolization of AECIIs. Compared with the air group, the hyperoxia group showed a significantly increased apoptosis rate of AECIIs and signiifcantly increased mRNA and protein expression of GRP78, IRE1, XBP1, and CHOP compared at all time points (P<0.05). The hyperoxia group had signiifcantly greater lfuorescence intensity of CHOP than the air group at all time points. In the hyperoxia group, the protein expression of CHOP was positively correlated with the apoptosis rate of AECIIs and the protein expression of IRE1 and XBP1 (r=0.97, 0.85, and 0.88 respectively;P<0.05). ConclusionsHyperoxia induces apoptosis of AECIIs possibly through activating the IRE1-XBP1-CHOP pathway.关键词
内质网应激/凋亡/需肌醇酶1/C/EBP同源蛋白/肺泡Ⅱ型上皮细胞/大鼠Key words
Endoplasmic reticulum stress/Apoptosis/Inositol-requiring kinase 1/C/EBP homologous protein/Type II alveolar epithelial cell/Rats引用本文复制引用
鞠慧敏,卢红艳,张燕雨,王秋霞,张强..需肌醇酶1介导的内质网应激通路参与高氧所致早产大鼠肺泡Ⅱ型上皮细胞凋亡[J].中国当代儿科杂志,2016,18(9):867-873,7.基金项目
国家自然科学基金面上项目(81370746);镇江市社会发展项目(SH2015071)。 ()