Kumar Vasantha H S, Chaker El Khoury Joseph, Gronostajski Richard, Wang Huamei, Nielsen Lori, Ryan Rita M
Department of Pediatrics, University at Buffalo, Buffalo, New York
Department of Pediatrics, Virginia Commonwealth University, Richmond, Virginia.
Physiol Rep. 2017 Aug;5(16). doi: 10.14814/phy2.13398.
Nuclear Factor I ( genes encode transcription factors essential for the development of organ systems including the lung. null mice die at birth with immature lungs. hemizygous mice have reduced lung maturation with decreased survival. We therefore hypothesized that these mice would be more sensitive to lung injury and would have lower survival to hyperoxia. Adult hemizygous mice and their wild-type (Wt) littermates were exposed to 100% O for 89, 80, 72 and 66 h for survival studies with lung outcome measurements at 66 h. hemizygous and Wt controls were also studied in RA at 66 h. Cell counts and cytokines were measured in bronchoalveolar lavage (BAL); lung sections examined by histopathology; lung angiogenic and oxidative stress gene expression assessed by real-time PCR Unexpectedly, hemizygous mice (0/14-0%) had significantly lower mortality compared to Wt mice (10/22-45%) at 80 h of hyperoxia ( < 0.003). LD was 80 h in the Wt group versus 89 h in the hemizygous group. There were no differences in BAL cell counts between the groups. Among the cytokines studied, MIP-2 was significantly lower in hemizygous mice exposed to hyperoxia. New vessel formation, edema, congestion, and alveolar hemorrhage were noted on histopathology at 72 and 80 h in wild-type mice. hemizygous lungs had significant downregulation of genes involved in redox signaling and inflammatory pathways. Adult hemizygous mice are relatively resistant to hyperoxia compared to wild-type littermates. Mechanisms contributing to this resistance are not clear; however, transcription factors such as may regulate cell survival and play a role in modulating postnatal lung development.
核因子I（基因编码对包括肺在内的器官系统发育至关重要的转录因子。基因敲除小鼠出生时因肺发育不成熟而死亡。半合子小鼠肺成熟度降低，存活率下降。因此，我们推测这些小鼠对肺损伤更敏感，在高氧环境下存活率更低。成年半合子小鼠及其野生型（Wt）同窝小鼠暴露于100%氧气中89、80、72和66小时进行存活研究，并在66小时时测量肺结局指标。在66小时时，也对半合子和Wt对照组进行类风湿关节炎研究。在支气管肺泡灌洗（BAL）中测量细胞计数和细胞因子；通过组织病理学检查肺切片；通过实时PCR评估肺血管生成和氧化应激基因表达。出乎意料的是，在高氧80小时时，半合子小鼠（0/14 - 0%）的死亡率显著低于Wt小鼠（10/22 - 45%）（P < 0.003）。Wt组的半数致死时间为80小时，而半合子组为89小时。两组之间的BAL细胞计数没有差异。在所研究的细胞因子中，暴露于高氧的半合子小鼠中的巨噬细胞炎性蛋白-2显著降低。在72和80小时时，野生型小鼠的组织病理学显示有新血管形成、水肿、充血和肺泡出血。半合子肺中参与氧化还原信号传导和炎症途径的基因有显著下调。与野生型同窝小鼠相比，成年半合子小鼠对高氧相对具有抗性。导致这种抗性的机制尚不清楚；然而，诸如核因子I等转录因子可能调节细胞存活并在调节出生后肺发育中发挥作用。
