N-acetylcysteine attenuates the maternal and fetal proinflammatory response to intrauterine LPS injection in an animal model for preterm birth and brain injury
N-acetylcysteine attenuates the maternal and fetal proinflammatory response to intrauterine LPS injection in an animal model for preterm birth and brain injury
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DOI：
10.3109/14767058.2010.528089
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发表时间：
2011-05-01
影响因子：
1.8
通讯作者：
Singh, Inderjit
中科院分区：
文献类型：
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作者：
Chang, Eugene Y.;Zhang, Jingmei;Singh, Inderjit
客观的。母体免疫激活（MIA）与早产（PTB）和异常神经系统结果相关。我们假设 N-乙酰半胱氨酸 (NAC) 作为抗炎剂可以减少 PTB 和新生儿脑损伤。方法。怀孕的 CD-1 小鼠在第 15/20 天接受宫内 LPS 或盐水。他们接受 NAC 或生理盐水，并在分娩前接受监测。对幼崽进行跟踪并在出生后第 1/30 天处死并收集大脑。对重链神经丝蛋白（NF-H）、髓磷脂碱性蛋白（MBP）和蛋白脂质蛋白（PLP）进行免疫染色。另一组在治疗后6小时处死动物，收集胎脑、胎盘和子宫肌层。测定IL-6、IL-1β、IL-10和肿瘤坏死因子(TNF)-αmRNA表达。采用非参数分析进行分析，适当时进行两两比较。结果。脂多糖 (LPS) 引起 PTB（79 vs. 0%，p < 0.005），NAC 可减少 PTB [0.45（95% CI：0.26-0.83），p < 0.008]。 LPS 增加子宫肌层和胎盘中 IL-6 的表达。这种现象被子宫肌层中的 NAC 减弱。 LPS 处理后胎儿大脑中 IL-1β、IL-6 和 TNF-α 的表达增加。 LPS 产生改变的 NF-H、MBP 和 PLP 染色，并且这些影响被 NAC 减弱。结论。 NAC 可以减轻 MIA 模型中的炎症并减少 PTB 和白质损伤。它是预防 PTB 和神经损伤研究的一个有趣的候选者。
Objective. Maternal immune activation (MIA) is associated with preterm birth (PTB) and abnormal neurologic outcome. We hypothesized that N-acetylcysteine (NAC) would decrease PTB and neonatal brain injury acting as an anti-inflammatory.Methods. Pregnant CD-1 mice received intrauterine LPS or saline on day 15/20. They received NAC or saline and were monitored until delivery. Pups were followed and sacrificed on postnatal days 1/30 and brains were collected. Immunostaining for heavy-chain neurofilament protein (NF-H), myelin basic protein (MBP), and proteolipid protein (PLP) was performed. In another group, animals were sacrificed 6 h after treatment, and fetal brain, placenta, and myometrium were collected. Il-6, Il-1 beta, Il-10, and tumor necrosis factor (TNF)-alpha mRNA expression was determined. Nonparametric analysis was used for analysis, and pairwise comparisons were performed when appropriate.Results. Lipopolysaccharide (LPS) caused PTB (79 vs. 0%, p < 0.005), and this was reduced by NAC [0.45 (95% CI: 0.26-0.83), p < 0.008]. LPS increased IL-6 expression in myometrium and placenta. This was attenuated by NAC in myometrium. IL-1 beta, IL-6, and TNF-alpha expression increased in the fetal brain with LPS. LPS produced altered NF-H, MBP, and PLP staining, and these effects were attenuated by NAC.Conclusion. NAC attenuates inflammation in this MIA model and reduces PTB and white matter injury. It is an interesting candidate for study for prevention of PTB and neurologic injury.