Cigdem Murat Kemal, Kizil Goksel, Onen Abdurrahman, Kizil Murat, Nergiz Yusuf, Celik Yusuf
Department of Pediatric Surgery, Medical School, Dicle University, 21280, Diyarbakir, Turkey.
Pediatr Surg Int. 2010 Apr;26(4):401-6. doi: 10.1007/s00383-010-2552-2. Epub 2010 Feb 3.
BACKGROUND/PURPOSE: Many studies suggest a role for antioxidants in the prevention of lung hypoplasia in nitrofen-induced rat models with congenital diaphragmatic hernia (CDH). This study investigates the oxidative status and the histological outcome of prenatal administration of vitamins E and C with synergistic effect, and effect of N-acetylcysteine (NAC) to improve lung maturation of nitrofen-induced rats.
CDH was induced by maternal administration of a single oral dose of nitrofen on day 9.5 of gestation, and the Sprague-Dawley rats were randomly divided into five groups: nitrofen (N), nitrofen + vitamin C (NC), nitrofen + vitamin E (NE), nitrofen + vitamin C + vitamin E (NCE) and nitrofen + NAC (NNAC). A control group in which only vehicle was administered was included. Cesarean section was performed on day 21. Body weight (BW) and total lung weight (LW) of all fetuses with CDH were recorded; lung histological evaluation was performed, and protein content of lungs, determination of thiobarbituric acid reactive substances, and the protein carbonyls in tissue samples were determined.
A total of 133 rat fetuses with CDH were investigated. The body weight and the lung weight of fetuses of all groups that were exposed to nitrofen were significantly decreased than of the control group (P < 0.05). The animals exposed to nitrofen with different antioxidants showed increased protein levels in lung tissue. However, in the NCE and the NNAC groups, protein levels were significantly increased than in the others. Malondialdehyde levels significantly decreased in the NCE and the NNAC groups when compared with the NC and the NE groups. In addition, the NCE and NNAC groups decreased protein oxidation to control levels, and no significant difference was observed between control and these two antioxidants groups. The N, NC, NE and NNAC groups showed minimal improvement in lung histology; the NCE groups showed the most improvement in lung histology when compared with the other nitrofen plus antioxidant groups.
Prenatal administration of NAC and vitamin E in combination with vitamin C represented the best effects to avoid oxidative damage and protein content of the lungs in rat pups with CDH at birth.
背景/目的：许多研究表明抗氧化剂在预防硝呋烯腙诱导的先天性膈疝（CDH）大鼠模型的肺发育不全中发挥作用。本研究调查了具有协同作用的维生素E和维生素C产前给药后的氧化状态和组织学结果，以及N-乙酰半胱氨酸（NAC）对改善硝呋烯腙诱导大鼠肺成熟的作用。
在妊娠第9.5天通过母体单次口服硝呋烯腙诱导CDH，将Sprague-Dawley大鼠随机分为五组：硝呋烯腙组（N）、硝呋烯腙+维生素C组（NC）、硝呋烯腙+维生素E组（NE）、硝呋烯腙+维生素C+维生素E组（NCE）和硝呋烯腙+NAC组（NNAC）。设立仅给予赋形剂的对照组。在第21天进行剖宫产。记录所有患有CDH胎儿的体重（BW）和肺总重量（LW）；进行肺组织学评估，并测定肺组织蛋白含量、硫代巴比妥酸反应性物质以及组织样本中的蛋白质羰基。
共研究了133只患有CDH的大鼠胎儿。所有暴露于硝呋烯腙的组的胎儿体重和肺重量均显著低于对照组（P<0.05）。暴露于硝呋烯腙并给予不同抗氧化剂的动物肺组织中的蛋白水平升高。然而，在NCE组和NNAC组中，蛋白水平显著高于其他组。与NC组和NE组相比，NCE组和NNAC组中的丙二醛水平显著降低。此外，NCE组和NNAC组将蛋白质氧化降低至对照水平，在对照组与这两个抗氧化剂组之间未观察到显著差异。N组、NC组、NE组和NNAC组在肺组织学方面改善最小；与其他硝呋烯腙加抗氧化剂组相比，NCE组在肺组织学方面改善最大。
产前给予NAC以及维生素E与维生素C联合应用对避免出生时患有CDH的幼鼠肺部的氧化损伤和蛋白质含量具有最佳效果。
