The expression and effect of TRF1 and TRF2 in neonatal rats with bronchopulmonary dysplasia / 国际儿科学杂志

ABSTRACT

Objective To investigate the dynamic expression of telomere repeat binding factor 1 (TRF1) and telomeric repeat binding factor 2 (TRF2) in the development and progression of bronchopulmonary dysplasia (BPD) in neonatal rats and to clarify its role in BPD alveolar dysplasia.Methods The neonatal rat BPD model (n =40) was induced by using neonatal SD rats with inhaled oxygen concentration of 85％.The control group was prepared by inhaled air (n =40).In the two groups,10 rats were randomly selected from 1 day,3 days,7 days,and 14 days after the experiment.The lung tissue samples were collected,HE staining was performed to observe the pathological changes,and the alveolar development degree was evaluated by radial alveolar counting (RAC).Immunohistochemistry was used to observe the localization and expression of TRF1 and TRF2.Western Blot and real-time quantitative PCR (RT-PCR) were used to detect the expression levels of TRF1 and TRF2 proteins and genes in lung tissue.Results Immunohistochemical staining showed that TRF1 was mainly localized in the nucleus of alveolar epithelial cells and bronchial epithelial cells.TRF2 protein was found in the nucleus and cytoplasm of alveolar epithelial cells and bronchial epithelial cells.The expression was significantly higher than that of the control group.Compared with the control group,the TRF1 and TRF2 proteins increased significantly from 1d (TRF1 in control group:0.163 ±0.022,in model group:0.251 ±0.022;TRF2 in control group:0.156 ±0.012,in model group:0.240 ±0.018) to 14d (TRF1 in control group:0.193 ± 0.024,in model group:0.230 ± 0.025;TRF2 in control group:0.225 ± 0.017,in model group:0.350 ±0.012) rather than the control group (P ＜ 0.05).The mRNA expression levels of TRF1 and TRF2 increased continuously from 1d to 7d of hyperoxia exposure (TRF1 in control group:0.946 ± 0.028,in model group:1.590 ± 0.228;TRF2 in control group:0.834 ± 0.083,in model group:1.783 ±0.262) and decreased at 14d (TRF1 in control group:2.217 ± 0.225,in model group:1.259 ± 0.217,P＜0.05;TRF2 in control group:2.143 ±0.250,in model group:0.997 ±0.199,P ＜0.05).Conclusion In the developmental stage of BPD,TRF1 and TRF2 act as negative regulators of telomere length,and protein levels are up-regulated,which suggest that they be involved in the pathological process of BPD alveolar dysplasia.