目的：通过检测内质网应激（ERS）相关因子葡萄糖调节蛋白（GRP78）及C/EBP同源蛋白（CHOP）在支气管肺发育不良（BPD）大鼠肺组织中的表达及其与肺泡上皮细胞凋亡的关系，探讨ERS介导肺泡上皮细胞凋亡在BPD发病机制中的作用。方法将24只新生SD大鼠随机分为对照组和BPD组，每组12只。BPD组大鼠暴露于85%高氧中，对照组大鼠置于空气中。在实验7、14和21天每组各处死4只大鼠，通过免疫组化检测GRP78在肺组织中的表达和分布，实时定量PCR（real-time PCR）和免疫印迹（Western blot）技术检测GRP78及CHOP的表达变化，原位末端标记（TUNEL）法检测肺组织细胞凋亡。结果在各时间点，BPD组肺组织的细胞凋亡数，GRP78、CHOP mRNA及蛋白表达与对照组相比，差异有统计学意义（P均<0.01）。随时间延长，BPD组肺组织的细胞凋亡数，GRP78、CHOP mRNA及蛋白表达水平呈上升趋势，差异有统计学意义（P均<0.01）。结论高氧可启动ERS并可能通过激活CHOP通路介导肺泡上皮细胞凋亡，参与BPD的发病过程。%Objectives To investigate the expressions of endoplasmic reticulum stress (ERS)-related factors, glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), in lungs of rats with bronchopulmonary dysplasia (BPD) and their relationship with pneumonocyte apoptosis, and further to explore the role of ERS-induced apoptosis in the pathogen-esis of BPD. Methods A total of 24 neonatal SD rats were randomly divided into control group and BPD group with 12 rats each. Rats in BPD group were exposed to 85%O2, while rats in the control group were exposed to air. Four rats in each group were sacriifced at 7, 14 and 21 days respectively after exposure. The expression of GRP78 in the lung tissues was examined by immunohistochemistry, the mRNA and protein levels of GRP78 and CHOP were detected respectively by real-time PCR and Western blot, and the apoptosis in lung cells were evaluated by TdT-mediated dUTP nick end labeling (TUNEL) assay. Results The mRNA and protein levels of GRP78 and CHOP, and the cell apoptosis in BPD group were signiifcantly different from those in control group (P<0.01) at different time points and increased over the time of hyperoxic exposure (P<0.01). Conclusions En-doplasmic reticulum stress may be initiated by hyperoxic exposure and apoptosis is induced via CHOP signal pathway, which is involved in the pathogenesis of BPD.
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