Ito Masato, Nagano Nobuhiko, Arai Yukio, Ogawa Ryo, Kobayashi Shingo, Motojima Yukiko, Go Hayato, Tamura Masanori, Igarashi Kazuhiko, Dennery Phyllis A, Namba Fumihiko
Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan.
Pediatr Res. 2017 Jun;81(6):926-931. doi: 10.1038/pr.2017.17. Epub 2017 Jan 18.
BTB and CNC homology 1 (Bach1) is a transcriptional repressor of heme oxygenase (HO)-1. The effects of Bach1 disruption on hyperoxic lung injury in newborn mice have not been determined. We aimed to investigate the role of Bach1 in the newborns exposed to hyperoxia.
Bach1 and WT newborn mice were exposed to 21% or 95% oxygen for 4 d and were then allowed to recover in room air. Lung histology was assessed and lung Bach1, HO-1, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 mRNA levels were evaluated using RT-PCR. Lung inflammatory cytokine levels were determined using cytometric bead arrays.
After 10 d recovery from neonatal hyperoxia, Bach1 mice showed improved lung alveolarization compared with WT. HO-1, IL-6, and MCP-1 mRNA levels and IL-6 and MCP-1 protein levels were significantly increased in the Bach1 lungs exposed to neonatal hyperoxia. Although an increase in apoptosis was observed in the Bach1 and WT lungs after neonatal hyperoxia, there were no differences in apoptosis between these groups.
Bach1 newborn mice were well-recovered from hyperoxia-induced lung injury. This effect is likely achieved by the antioxidant/anti-inflammatory activity of HO-1 or by the transient overexpression of proinflammatory cytokines.
BTB和CNC同源蛋白1（Bach1）是血红素加氧酶（HO）-1的转录抑制因子。Bach1缺失对新生小鼠高氧肺损伤的影响尚未明确。我们旨在研究Bach1在暴露于高氧环境的新生儿中的作用。
将Bach1基因敲除小鼠和野生型新生小鼠暴露于21%或95%氧气环境中4天，然后置于室内空气中恢复。评估肺组织学情况，并使用逆转录聚合酶链反应（RT-PCR）评估肺组织中Bach1、HO-1、白细胞介素（IL）-6和单核细胞趋化蛋白（MCP）-1的mRNA水平。使用细胞计数珠阵列测定肺组织炎症细胞因子水平。
新生小鼠高氧暴露10天后恢复，与野生型小鼠相比，Bach1基因敲除小鼠的肺泡化得到改善。暴露于新生小鼠高氧环境的Bach1基因敲除小鼠肺组织中，HO-1、IL-6和MCP-1的mRNA水平以及IL-6和MCP-1的蛋白水平显著升高。虽然新生小鼠高氧暴露后，Bach1基因敲除小鼠和野生型小鼠肺组织中的细胞凋亡均增加，但两组之间的细胞凋亡无差异。
Bach1基因敲除新生小鼠能很好地从高氧诱导的肺损伤中恢复。这种作用可能是通过HO-1的抗氧化/抗炎活性或促炎细胞因子的短暂过度表达实现的。
