Sluiter W, Bos A P, Silveri F, Tenbrinck R, Kraakslee R, Tibboel D, Koster J F, Molenaar J C
Department of Biochemistry I, Eramus University, Rotterdam, The Netherlands.
Pediatr Res. 1992 Oct;32(4):394-8. doi: 10.1203/00006450-199210000-00005.
We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.
我们建立了先天性膈疝（CDH）实验大鼠模型，以阐明这种严重先天性异常在人类中的病因和发病机制，特别是研究短期人工通气对CDH肺抗氧化防御机制的影响。在孕期，通过母体接触2,4-二氯苯基对硝基苯醚（除草醚），约60%的后代诱发了CDH。这种除草剂在化学结构上类似于甲状腺激素。检测胎鼠（第19、20、21和22天）肺组织的蛋白质和DNA含量以及超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶（GPX）的活性。在短期5小时内，对气管切开的新生大鼠进行压力控制的人工通气，分别使用室内空气或纯氧，评估相同参数。在CDH大鼠和对照组中，肺湿重均在妊娠期增加。足月时，CDH大鼠的平均肺重显著低于对照组。两组在出生前和出生时每毫克肺组织的蛋白质和DNA含量以及超氧化物歧化酶、过氧化氢酶和GPX活性均无差异。新生大鼠经空气和纯氧人工通气后，CDH肺中超氧化物歧化酶活性有下降趋势，而过氧化氢酶活性基本不变。然而，经空气通气后足月时CDH肺中GPX活性降至初始活性的80%，经纯氧通气后降至70%。在该动物模型中，短期人工通气后GPX活性下降的这一发现可能表明CDH新生大鼠有发生氧相关性肺损伤的风险。
