Department of Pediatrics and Ophthalmology, Division of Neonatal-Perinatal Medicine Clinical and Translational Research Labs, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Box 49, Brooklyn, NY, 11203, USA.
Department of Ophthalmology, State University of New York, Downstate Medical Center, Brooklyn, NY, 11203, USA.
Respir Res. 2021 Jul 5;22(1):196. doi: 10.1186/s12931-021-01786-w.
Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats.
Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O with brief hypoxia (12% O); or (2) room air (RA) with brief hypoxia (12% O), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants.
Of the two neonatal IH paradigms 21%/12% O IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities.
Data suggest that higher FiO may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.
新生儿间歇性低氧（IH）导致早产儿未成熟抗氧化系统产生氧化应激，导致肺损伤。辅酶 Q10（CoQ10）和鱼油可预防氧化损伤。我们检验了这样一个假设，即在新生大鼠中，CoQ10 比鱼油更能预防 IH 诱导的肺损伤。
出生时（P0），新生大鼠经历两种临床相关的 IH 模型：（1）50% O2 伴有短暂低氧（12% O2）；或（2）RA 伴有短暂低氧（12% O2），直到 P14 日，在此期间，它们每天口服 CoQ10、鱼油或橄榄油进行补充，从 P0 至 P14 日。在 P14 日时对幼鼠进行研究，或在没有进一步治疗的情况下置于 RA 中直至 P21 日。评估肺的组织病理学和形态计量学；氧化应激和脂质过氧化的生物标志物；以及抗氧化剂。
两种新生儿 IH 模型中，21%/12% O2 IH 导致最严重的后果，表现在组织病理学和形态计量学上。CoQ10 可有效保护肺结构，减少 IH 诱导的氧化应激生物标志物。相比之下，鱼油导致显著的不良后果，包括肺泡过度简化、出血、二次嵴形成减少和隔增厚。这与氧化剂和抗氧化剂活性升高有关。
数据表明，IH 发作之间需要更高的 FiO2 以遏制 IH 的破坏性影响，并为肺部提供必要的休息。鱼油补充的负面结果表明氧化应激诱导的脂质过氧化。
