Ma Di, Gao Wenhui, Liu Junjiao, Kong Dan, Zhang Yunfeng, Qian Min
The second Hospital of Jilin University, Neonatal Department, Changchun, Jilin, China.
Medicine (Baltimore). 2020 Jun 26;99(26):e20433. doi: 10.1097/MD.0000000000020433.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in premature infants and is one of the leading causes of disability and death in newborns. The Keap-1/Nrf2 signaling pathway plays an important role in antioxidant and anti-inflammatory.Ten clean-grade, healthy pregnant Sprague-Dawley rats (purchased from Experimental Animal Center of Peking university, China) naturally gave birth to 55 neonatal rats from which 40 were selected and randomly divided into a hyperoxia group and a control group (N = 20, each). Thirty-two BPD patient samples are from Neonatal Department of the second Hospital of Jilin University from November 30, 2016 to May 1 2019.In present study, we observed that lung tissues of the control group did not undergo obvious pathological changes, whereas in the hyperoxia group, lung tissues had disordered structures. With increased time of hyperoxia exposure, the alveolar wall became attenuated. Under hypoxia conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in lung samples was significantly lower than that before treatment. The expression level of Keap1 mRNA and protein in the hyperoxia group was slightly lower than that of control group. The expression of Nrf2 and HO-1 mRNA and protein in the hyperoxia group was significantly higher than that of control group. For the infants with BPD, we found that the activity of SOD, GSH-Px, and CAT was significantly different from those of control group.We constructed a premature BPD animal model and found the abnormal of oxidative stress in different groups and the expression levels of Keap1/Nrf2 signaling pathway-related molecules, and we validated the results in premature infants with BPD.
支气管肺发育不良(BPD)是一种常见于早产儿的慢性肺部疾病,是新生儿致残和死亡的主要原因之一。Keap-1/Nrf2信号通路在抗氧化和抗炎方面发挥着重要作用。十只清洁级健康的Sprague-Dawley孕鼠(购自中国北京大学实验动物中心)自然分娩出55只新生大鼠,从中选取40只并随机分为高氧组和对照组(每组N = 20)。32例BPD患者样本来自吉林大学第二医院新生儿科2016年11月30日至2019年5月1日期间的病例。在本研究中,我们观察到对照组的肺组织未发生明显的病理变化,而高氧组的肺组织结构紊乱。随着高氧暴露时间的增加,肺泡壁变薄。在缺氧条件下,肺样本中氧化应激相关酶(CAT、GSH-Px、SOD)的活性显著低于治疗前。高氧组中Keap1 mRNA和蛋白的表达水平略低于对照组。高氧组中Nrf2和HO-1 mRNA及蛋白的表达显著高于对照组。对于BPD婴儿,我们发现其SOD、GSH-Px和CAT的活性与对照组有显著差异。我们构建了早产BPD动物模型,发现不同组中氧化应激异常以及Keap1/Nrf2信号通路相关分子的表达水平,并在早产BPD婴儿中验证了结果。