Department of Pediatrics, University at Buffalo, Buffalo, NY, USA.
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
J Neonatal Perinatal Med. 2021;14(1):53-60. doi: 10.3233/NPM-200483.
Oxygen toxicity mediated by reactive oxygen species (ROS) plays an essential role in the development of bronchopulmonary dysplasia in premature infants. By reducing oxidative stress, antioxidants protect the immature lung. We studied the effects of MnTBAP, a catalytic antioxidant on angiogenesis and alveolar growth following neonatal hyperoxia.
Newborn mouse litters randomized to room air (RA) or >95% O2 for 72 hours from day 4 (D4) to D7 to receive either MnTBAP (10 mg/kg/d) or saline intraperitoneally (every 24 h for three doses). Lungs harvested for angiogenic gene expression, protein expression, and histopathology post-hyperoxia exposure. Radial alveolar count (RAC), mean linear intercept (MLI) and vessel density assessed by histopathology.
Angiogenic gene expression was significantly lower in the hyperoxia group compared to the RA group. The protein expression for VEGF and its receptor, VEGFR1, was significantly lower following treatment with MnTBAP compared to hyperoxia alone. Expression of VEGFR2, Angiopoietin-1 and TIE2, were substantially higher in the RA groups compared to hyperoxia groups with or without MnTBAP. Hyperoxia groups demonstrated alveolar simplification. MnTBAP reduced vessel density and failed to improve alveolar growth following hyperoxia.
MnTBAP, a catalytic antioxidant, does not offer protection from hyperoxia-induced alveolar impairment. The lack of angiogenic upregulation by MnTBAP may contribute to alveolar simplification in newborn mice.
活性氧（ROS）介导的氧毒性在早产儿支气管肺发育不良的发展中起着至关重要的作用。抗氧化剂通过降低氧化应激来保护未成熟的肺。我们研究了 MnTBAP（一种催化抗氧化剂）在新生期高氧后血管生成和肺泡生长中的作用。
新生鼠随机分为空气组（RA）或 95%以上的 O2 组，从第 4 天（D4）至第 7 天（D7）持续 72 小时，接受 MnTBAP（10mg/kg/d）或腹腔内生理盐水（每 24 小时一次，共三次）。高氧暴露后，采集肺组织进行血管生成基因表达、蛋白表达和组织病理学检查。通过组织病理学评估径向肺泡计数（RAC）、平均线性截距（MLI）和血管密度。
与 RA 组相比，高氧组的血管生成基因表达明显降低。与单独高氧组相比，MnTBAP 处理后 VEGF 及其受体 VEGFR1 的蛋白表达明显降低。RA 组的 VEGFR2、血管生成素 1 和 TIE2 的表达明显高于高氧组，无论是否用 MnTBAP 处理。高氧组表现为肺泡简化。MnTBAP 降低了血管密度，并不能改善高氧后肺泡的生长。
MnTBAP，一种催化抗氧化剂，不能提供对高氧诱导的肺泡损伤的保护。MnTBAP 缺乏血管生成的上调可能导致新生小鼠肺泡简化。
