Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect
Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect
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怀孕期间补充锌可通过其抗炎作用防止脂多糖引起的胎儿生长受限和死亡
DOI：
10.4049/jimmunol.1103579
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发表时间：
2012-07-01
影响因子：
4.4
通讯作者：
Xu, De-Xiang
中科院分区：
文献类型：
--
作者：
Chen, Yuan-Hua;Zhao, Mei;Xu, De-Xiang
LPS与不良发育结果相关，包括早产、胎儿死亡、致畸性和宫内生长受限（IUGR）。以前的报告表明，锌保护免受LPS诱导的致畸性。在本研究中，我们调查了孕期补锌对LPS诱导的早产、胎儿死亡和IUGR的影响。从妊娠第15天（GD）至GD 17天，除对照组外，所有妊娠小鼠每天腹腔注射LPS（75 μg/kg）。在整个妊娠期间，通过饮用水（每升75 mg元素锌）给一些妊娠小鼠施用硫酸锌。正如预期，从GD 15至GD 17每天腹腔注射LPS导致36.4%（4/11）的母兽在GD 18前分娩。在完成妊娠的母鼠中，63.2%的胎儿死亡。此外，LPS显着降低胎儿体重和顶臀长度。有趣的是，在怀孕期间补充锌可以保护小鼠免受LPS诱导的早产和胎儿死亡。此外，补锌可显著减轻LPS引起的IUGR和骨骼发育迟缓。进一步的实验表明，补锌显著减弱LPS诱导的胎盘炎性细胞因子和环氧合酶-2的表达。补充锌也显著减弱LPS诱导的迷路区单核窦状滋养层巨细胞NF-κB和MAPK信号的激活。它也抑制LPS诱导的胎盘AKT磷酸化。总之，在怀孕期间补充锌通过其抗炎作用防止LPS诱导的胎儿生长受限和死亡。
LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown–rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.