Ozkan K Uğur, Ozokutan B Hayri, Inanç Fatma, Boran Cetin, Kilinç Metin
Department of Pediatric Surgery, Kahramanmaraş Imam University Medical Faculty, 46050, Turkey.
J Pediatr Surg. 2005 Mar;40(3):484-8. doi: 10.1016/j.jpedsurg.2004.11.040.
BACKGROUND/PURPOSE: The aim of this study was to evaluate the effects of maternal nicotine exposure during gestation on injury severity of small intestine in the newborn rats subjected to hypoxia-reoxygenation and cold stress.
A total of 21 Sprague-Dawley pregnant rats were divided into 3 equal groups. The groups were labeled as group 1, control group; group 2, hypoxia-reoxygenation group; and group 3, nicotine-hypoxia-reoxygenation group. The rats of group 3 were exposed to nicotine via subcuticular injection for the last week of gestation (2 mg/kg/d). Newborn rats were collected immediately after birth to prevent suckling of maternal milk (40 rat pups in group 1, 43 rat pups in group 2, and 41 rat pups in group 3). Litters in groups 2 and 3 were stressed twice daily with asphyxia followed by cold (4 degrees C for 10 minutes) stress to induce hypoxic intestinal injury which is relevant to human necrotizing enterocolitis. Breathing 100% CO2 for 10 minutes in a chamber followed by 10-minute 100% O2 breathing was the asphyxia model repeated twice daily. After hypoxia-reoxygenation and cold stress, newborn rats were returned to their mother's cages. This protocol was repeated for the following 2 days, and the rat pups were decapitated on the third day. Using this protocol of asphyxia and cold stress, all of neonatal rats developed clinical and pathological signs of hypoxia-induced intestinal injury. The entire gastrointestinal tract was removed and examined macroscopically. A 2-cm section of distal ileum from each animal was taken for histopathological and biochemical examinations. Histological changes in ileal architecture were scored and graded from 1 to 5. The remaining intestinal tissues of the animals were used for lipid peroxidation analysis.
Typical signs of hypoxia-induced intestinal injury were observed in the 2 experimental groups (groups 2 and 3) macroscopically. There were more grades 3 and 4 injuries in group 3 (P < .05). The malondialdehyde levels were elevated in groups 2 and 3 (P < .001). The malondialdehyde levels of the group 3 were also significantly higher than group 2 (P < .01).
Maternal nicotine exposure during gestation results in higher grade histological injury in newborn rats subjected to hypoxia-reoxygenation and cold stress.
背景/目的:本研究旨在评估孕期母体尼古丁暴露对经历缺氧复氧和冷应激的新生大鼠小肠损伤严重程度的影响。
将21只Sprague-Dawley孕鼠平均分为3组。第1组为对照组;第2组为缺氧复氧组;第3组为尼古丁-缺氧复氧组。第3组孕鼠在妊娠最后一周通过皮下注射给予尼古丁(2毫克/千克/天)。新生大鼠出生后立即收集,以防止吸食母乳(第1组40只幼鼠,第2组43只幼鼠,第3组41只幼鼠)。第2组和第3组的幼鼠每天进行两次应激,先进行窒息然后进行冷应激(4℃,持续10分钟),以诱导与人类坏死性小肠结肠炎相关的缺氧性肠损伤。在一个舱室内呼吸100%二氧化碳10分钟,然后呼吸100%氧气10分钟,此窒息模型每天重复两次。缺氧复氧和冷应激后,将新生大鼠放回其母鼠笼中。此方案在接下来的2天重复进行,第3天对幼鼠进行断头处理。采用此窒息和冷应激方案,所有新生大鼠均出现缺氧性肠损伤的临床和病理体征。取出整个胃肠道并进行宏观检查。从每只动物的回肠末端取2厘米长的一段进行组织病理学和生化检查。对回肠结构的组织学变化进行评分并分为1至5级。动物的其余肠道组织用于脂质过氧化分析。
在2个实验组(第2组和第3组)宏观上观察到缺氧性肠损伤的典型体征。第3组中3级和4级损伤更多(P <.05)。第2组和第3组丙二醛水平升高(P <.001)。第3组的丙二醛水平也显著高于第2组(P <.01)。
孕期母体尼古丁暴露会导致经历缺氧复氧和冷应激的新生大鼠出现更高级别的组织学损伤。