摘要
目的探讨小泛素相关修饰物(SUMO)化修饰CCAAT增强子结合蛋白α(C/EBPα)在支气管肺发育不良(BPD)早产大鼠中的表达及其作用。方法将18只早产大鼠随机分为空气组和高氧组(n=9),建立高氧暴露早产大鼠BPD模型。分别在4 d、7 d及14 d,每组各取3只大鼠采集肺组织,糖原染色观察肺组织分化情况;免疫组化检测Ki67表达;Western blot检测SUMO1及C/EBPα蛋白表达;免疫共沉淀检测SUMO化C/EBPα表达。结果与同时间点空气组相比,高氧组大鼠肺组织糖原染色强度4 d时减弱,7 d及14 d时明显增强;随高氧暴露时间延长,高氧组大鼠肺组织中Ki67表达逐渐升高,且均高于同时间点空气组;与空气组相比,高氧组C/EBPα蛋白4 d时表达增加,7 d及14 d时表达降低(P<0.05);高氧组SUMO1及SUMO化C/EBPα蛋白表达呈逐渐上升趋势,均明显高于同时间点空气组(P<0.05)。高氧组SUMO化C/EBPα表达与糖原染色强度及核增殖抗原Ki67均呈正相关(r=0.529、0.671,P<0.05)。结论高氧暴露所致早产大鼠BPD模型中,肺泡上皮细胞过度增殖与分化障碍可能与SUMO化C/EBPα表达增加相关。
Objective 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. Methods 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. Results 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）. Conclusions 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/EBPα.
作者
朱玥
卢红艳
郝晓波
常明
王秋霞
万峰云
万雪晴
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)
出处
《中国当代儿科杂志》
CAS
CSCD
北大核心
2018年第5期403-409,共7页
Chinese Journal of Contemporary Pediatrics
基金
国家自然科学基金(81741052)
江苏省自然科学基金(BK20161356)
