Aras-López Rosa, Almeida L, Andreu-Fernández V, Tovar J, Martínez L
Congenital Malformations Lab, Institute of Medicine and Molecular Genetic (INGEMM), Institute for Health Research of La Paz Universitary Hospital (IdiPAZ), Madrid, Spain.
BCNatal, Barcelona Center for Maternal-Fetal Medicine and Neonatology, Hospital Clinic and Hospital San Joan de Deu, IdiBaps, University of Barcelona, Barcelona, Spain.
Pediatr Surg Int. 2018 Mar;34(3):307-313. doi: 10.1007/s00383-017-4201-5. Epub 2017 Oct 27.
To evaluate if the redox system is unbalanced in the hearts of nitrofen-induced congenital diaphragmatic hernia (CDH) animals and to study the possible preventive effects of two anti-oxidant treatments, apocynin and epigallocatechin-3-gallate (EGCG).
Adult rats were divided into four groups. Group 1: rats received only vehicle on day E9.5. Group 2: rats received 100 mg nitrofen on day E9.5. Group 3: 1 month before mating rats received apocynin 1.5 mM and, when pregnant, 100 mg nitrofen on day E9.5. Group 4: same than group 3 but with EGCG 30 mg/kg. All fetuses were recovered at term and the hearts were processed. Nox activity and mRNA levels of Nox1, Nox2, Nox4, SOD1, SOD2, SOD3, catalase, and GPX1 were analyzed. Nox, SOD, and Catalase activity and H2O2 production were also evaluated.
Nox activity, HO production and Nox1, Nox2, and Nox4 mRNA levels were increased in the hearts of fetuses with CDH. There were no changes in SOD1 levels, whereas those of SOD2, SOD3, catalase, and GPX1 mRNA were decreased. Apocynin and EGCG treatments attenuated the increment of Nox and SOD activities and HO production was only decreased by apocynin.
These findings suggest a possible preventive effect on the abnormal redox metabolism of anti-oxidant treatments in the hearts from rat fetuses with CDH. If the same occurs in humans, it could represent a potential tool in future prenatal treatment.
评估在硝呋烯腙诱导的先天性膈疝（CDH）动物模型中，心脏的氧化还原系统是否失衡，并研究两种抗氧化剂——阿朴吗啡和表没食子儿茶素-3-没食子酸酯（EGCG）的可能预防作用。
成年大鼠分为四组。第1组：大鼠在胚胎第9.5天仅接受赋形剂。第2组：大鼠在胚胎第9.5天接受100毫克硝呋烯腙。第3组：交配前1个月，大鼠接受1.5毫摩尔阿朴吗啡，怀孕时在胚胎第9.5天接受100毫克硝呋烯腙。第4组：与第3组相同，但使用30毫克/千克EGCG。所有胎儿足月取出，对心脏进行处理。分析Nox活性以及Nox1、Nox2、Nox4、SOD1、SOD2、SOD3、过氧化氢酶和GPX1的mRNA水平。还评估了Nox酶、超氧化物歧化酶（SOD）和过氧化氢酶活性以及过氧化氢（H2O2）的产生。
患有CDH的胎儿心脏中，Nox活性、H2O2产生以及Nox1、Nox2和Nox4的mRNA水平升高。SOD1水平无变化，但SOD2、SOD3、过氧化氢酶和GPX1的mRNA水平降低。阿朴吗啡和EGCG处理减弱了Nox和SOD活性的增加，只有阿朴吗啡降低了H2O2的产生。
这些发现表明抗氧化剂处理可能对患有CDH的大鼠胎儿心脏异常的氧化还原代谢具有预防作用。如果在人类中也如此，这可能成为未来产前治疗的一种潜在手段。
