Department of Pediatric Surgery, Shamir Medical Center, Zerifin, Israel.
Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel.
PLoS One. 2020 Jun 1;15(6):e0233612. doi: 10.1371/journal.pone.0233612. eCollection 2020.
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of neonates, especially premature neonates. To date, there is no prophylactic treatment against NEC, except breast milk and slow increase in enteral feeding, and there is no antenatal prophylaxis.
To assess possible protective effects of antenatal N-Acetyl Cysteine (NAC) against the intestinal pathophysiological changes associated with NEC in a rat model of NEC and against its associated mortality.
Newborn Sprague-Dawley rats were divided into 5 groups: control (n = 33); NEC (n = 32)-subjected to hypoxia and formula feeding for 4 days to induce NEC; NEC-NAC (n = 34)-with induced NEC and concomitant postnatal NAC administration; NAC-NEC (n = 33)-born to dams treated with NAC for the last 3 days of pregnancy starting at gestational age of 18 days, and then subjected to induced NEC after birth; NAC-NEC-NAC (n = 36)-subjected to induced NEC with both prenatal and postnatal NAC treatment. At day of life 5, weight and survival of pups in the different groups were examined, and pups were euthanized. Ileal TNF-α, IL-6, IL-1β, IL-10, NFkB p65, iNOS and cleaved caspase 3 protein levels (western blot) and mRNA expression (RT-PCR) were compared between groups.
Pup mortality was significantly reduced in the NAC-NEC-NAC group compared to NEC (11% vs. 34%, P<0.05). Ileal protein levels and mRNA expression of all injury markers tested except IL-10 were significantly increased in NEC compared to control. These markers were significantly reduced in all NAC treatment groups (NEC-NAC, NAC-NEC, and NAC-NEC-NAC) compared to NEC. The most pronounced decrease was observed in the NAC-NEC NAC group.
Antenatal NAC decreases injury markers and mortality associated with NEC in a rat model. Antenatal administration of NAC may present a novel approach for NEC prophylaxis in pregnancies with risk for preterm birth.
坏死性小肠结肠炎（NEC）是一种毁灭性的新生儿胃肠道疾病，尤其是早产儿。迄今为止，除了母乳喂养和逐渐增加肠内喂养外，尚无针对 NEC 的预防性治疗，也没有产前预防措施。
评估产前 N-乙酰半胱氨酸（NAC）对 NEC 大鼠模型中与 NEC 相关的肠道病理生理变化的可能保护作用及其相关死亡率。
将新生 Sprague-Dawley 大鼠分为 5 组：对照组（n=33）；NEC 组（n=32）-接受缺氧和配方喂养 4 天以诱导 NEC；NEC-NAC 组（n=34）-在出生后同时给予 NAC 治疗；NAC-NEC 组（n=33）-出生前 3 天接受 NAC 治疗的母鼠，然后在出生后接受诱导性 NEC；NAC-NEC-NAC 组（n=36）-在出生前和出生后均接受 NAC 治疗，然后接受诱导性 NEC。在出生后第 5 天，检查不同组的幼崽的体重和存活率，并对幼崽进行安乐死。通过蛋白质印迹（western blot）和逆转录聚合酶链反应（RT-PCR）比较各组回肠 TNF-α、IL-6、IL-1β、IL-10、NFkB p65、iNOS 和 cleaved caspase 3 蛋白水平（western blot）和 mRNA 表达（RT-PCR）。
与 NEC 组相比，NAC-NEC-NAC 组的幼崽死亡率显著降低（11%比 34%，P<0.05）。与对照组相比，NEC 组所有测试损伤标志物的回肠蛋白水平和 mRNA 表达均显著增加，除 IL-10 外。所有 NAC 治疗组（NEC-NAC、NAC-NEC 和 NAC-NEC-NAC）与 NEC 组相比，这些标志物均显著降低。在 NAC-NEC-NAC 组中观察到最明显的降低。
产前 NAC 可降低 NEC 大鼠模型中与 NEC 相关的损伤标志物和死亡率。产前给予 NAC 可能为具有早产风险的妊娠提供一种预防 NEC 的新方法。
