Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation
Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation
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DOI：
10.1067/mob.2003.112
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发表时间：
2003-01-01
影响因子：
9.8
通讯作者：
Weiner, CP
中科院分区：
文献类型：
--
作者：
Buhimschi, IA;Buhimschi, CS;Weiner, CP
目的：宫内和母体全身感染被认为是早产的原因。由此导致的早产与75%的婴儿死亡率和50%的长期神经障碍有关。我们假设，在炎症反应过程中产生的大量自由基转移到氧化状态的胎儿母体氧化还原平衡，危及胎儿。因此，如果我们的工作假设是正确的，选择性灭活自由基与N-乙酰半胱氨酸（NAC），抗氧化剂和谷胱甘肽（GSH）的前体，将改善与炎症相关的早产的结果。我们测试的方面，这一假设在早产和胎儿损伤（死亡）的动物模型研究设计：NAC（1克/公斤）口服给药C57 B1/6小鼠腹腔注射10微克脂多糖（LPS）或盐水溶液（CRL）在妊娠第1 - 6天。记录潜伏期（从注射到分娩第一只幼仔的时间）和胎仔活力。为了区分早产的影响与炎症的影响，并记录存活率的任何改善，在注射后3、6和16小时处死小鼠。结果：每只C57 B1/6 LPS处理的小鼠在显著更短的潜伏期后早产（LPS：16.8小时[95%CI 15.9-17.6] vs CRL：54.7小时[95%CI 43.8-65.5]）。NAC使LPS处理动物的潜伏期间隔加倍至35.2小时（95% CI 21.0-49.2）。LPS单独导致100%的死胎率。58%的胎儿在LPS后16小时已经死亡。相比之下，当给予NAC时，LIPS后16小时只有33%的胎儿死亡（P= 0.001）。LPS降低后，母体的LPS：26.3 nmol/mg [95%CI 19.9-32.8] vs CRL：41.3 nmol/mg [95%CI 34.7-47.9，P
OBJECTIVE: Intrauterine and maternal systemic infections are proposed causes of preterm labor. The resulting prematurity is associated with 75% of infant mortality,and 50% of long-term neurologic handicaps. We hypothesize that free radicals generated in large quantities during an inflammatory response shift the fetomaternal redox balance to an oxidative state, compromising the fetus. Thus, if our working hypothesis is correct, selective inactivation of free radicals with N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor, would improve the outcome of preterm deliveries associated with inflammation. We tested aspects of this hypothesis in an animal model of preterm labor and fetal damage (death).STUDY DESIGN: NAC (1 g/kg) was administered orally to C57Bl/6 mice injected intraperitoneally with either 10 mug lipopolysaccharide (LPS) or saline solution (CRL) on day 1 6 of gestation. The latency period (time from injection to delivery of the first pup) and fetal viability were recorded. To discriminate between an effect of prematurity from an effect of inflammation, and to document any improvement in survival, mice were killed at 3; 6, and 16 hours after injection. Maternal and fetal redox states were approximated by measuring hepatic GSH.RESULTS: Each C57Bl/6 LPS-treated mouse delivered prematurely after a significantly shorter latency period (LPS: 16.8 hours [95% CI 15.9-17.6] vs CRL: 54.7 hours [95% Cl 43.8-65.5]). NAC doubled the latency interval of LPS-treated animals to 35.2 hours (95% CI 21.0-49.2). LPS alone resulted in a 100% rate of stillbirth. Fifty-eight percent of fetuses were already dead 16 hours after LPS. In contrast, only 33% of fetuses were dead 16 hours after LIPS (P=.001) when NAC was given. LPS was followed by a reduction in maternal (LPS: 26.3 nmol/mg [95% CI 19.9-32.8] vs CRL: 41.3 nmol/mg [95% CI 34.7-47.9, P