Zhu Yue, Lu Hong-Yan, Hao Xiao-Bo, Chang Ming, Wang Qiu-Xia, Wan Feng-Yun, Wan Xue-Qing
Department of Pediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2018 May;20(5):403-409. doi: 10.7499/j.issn.1008-8830.2018.05.013.
To study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role.
Eighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα.
Compared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05).
Hyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.
研究小泛素相关修饰物修饰的CCAAT增强子结合蛋白α（C/EBPα）在高氧诱导的早产大鼠支气管肺发育不良（BPD）模型中的表达及其作用。
将18只早产大鼠随机分为空气组和高氧组（每组9只）。对暴露于高氧的早产大鼠制备BPD模型。分别在出生后第4、7和14天处死两组大鼠（每个时间点3只），并采集肺组织。采用高碘酸-希夫（PAS）染色观察大鼠肺组织的分化情况。通过免疫组织化学检测Ki67表达。采用蛋白质免疫印迹法检测小泛素相关修饰物-1（SUMO1）和C/EBPα的蛋白表达。进行免疫共沉淀试验检测SUMO修饰的C/EBPα的蛋白表达。
与空气组相比，高氧组在出生后第4天肺组织糖原含量降低，在出生后第7天和14天含量增加。在高氧暴露期间，高氧组在所有时间点肺组织中Ki67表达均高于空气组。与空气组相比，高氧组出生后第4天C/EBPα蛋白表达增加，出生后第7天和14天降低（P<0.05）。在所有时间点，高氧组SUMO1和SUMO修饰的C/EBPα表达均显著高于空气组（P<0.05）。在高氧组中，SUMO修饰的C/EBPα蛋白表达与糖原含量呈正相关（r=0.529，P<0.05），与Ki67表达呈正相关（r=0.671，P<0.05）。
高氧可能通过增加SUMO修饰的C/EBPα的表达，诱导早产大鼠BPD模型中肺泡上皮细胞过度增殖和分化紊乱。
