Maternally-administered lipopolysaccharide (LPS) increases tumor necrosis factor alpha in fetal liver and fetal brain: Its suppression by low-dose LPS pretreatment
Maternally-administered lipopolysaccharide (LPS) increases tumor necrosis factor alpha in fetal liver and fetal brain: Its suppression by low-dose LPS pretreatment
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母体给予的脂多糖（LPS）增加胎儿肝脏和胎儿大脑中的肿瘤坏死因子α：低剂量LPS预处理对其抑制作用
DOI：
10.1016/j.toxlet.2007.08.002
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发表时间：
2008-01-04
影响因子：
3.5
通讯作者：
Xu, De-Xiang
中科院分区：
文献类型：
--
作者：
Ning, Huan;Wang, Hua;Xu, De-Xiang
脂多糖（LPS）与不良发育结局相关，包括宫内胎儿死亡（IUFD）、宫内生长迟缓（IUGR）和神经损伤。在LPS模型中，肿瘤坏死因子α（TNF-α）是导致IUFD、IUGR和神经损伤的主要介质。在本研究中，我们研究了母体给予LPS对母体血清、羊水、胎儿肝脏和胎儿大脑中TNF-α的影响。将定时妊娠小鼠腹膜内（i. p.）在妊娠第17天注射单剂量LPS（500 μ g/kg）。如预期的，TNF-α在母血和羊水中明显升高，以响应LPS。虽然母体给予LPS也增加了胎肝和脑中TNF-α蛋白的水平，但在不同组之间观察到胎肝和脑中TNF-α mRNA水平无显著差异，表明胎肝和脑中增加的TNF-α蛋白可能从母体循环或羊水或胎盘转移。当孕鼠腹腔注射低剂量LPS（10 μ g/kg）后，在LPS（500 μ g/kg，i. p.）前4、12、24或48 h，母体血清和羊水中LPS诱导的TNF-α明显受到抑制。重要的是，低剂量LPS预处理也大大减弱了LPS诱导的胎肝和胎脑中TNF-α蛋白的增加。总之，这些结果表明，围产期暴露于低剂量LPS诱导降低敏感性，随后的LPS挑战。(c)2007年由Elsevier爱尔兰有限公司出版。
Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR) and neurological injury. In the LPS model, tumor necrosis factor alpha (TNF-alpha) is the major mediator leading to IUFD, IUGR and neurological injury. In the present study, we investigated the effect of maternally-administered LPS on TNF-alpha in maternal serum, amniotic fluid, fetal liver and fetal brain. The timed pregnant mice were intraperitoneally (i.p.) injected with a single dose of LPS (500 mu g/kg) on gestational day 17. As expected, TNF-alpha was obviously increased in maternal serum and amniotic fluid in response to LPS. Although maternally-administered LPS also increased the level of TNF-alpha protein in fetal liver and brain, no significant difference in TNF-alpha mRNA level in fetal liver and brain was observed among different groups, suggesting that the increased TNF-alpha protein in fetal liver and brain may be transferred from either the maternal circulation or amniotic fluid or placenta. When the pregnant mice were pretreated with a low-dose LPS (10 mu g/kg, i.p.) at 4, 12, 24 or 48 h before LPS (500 mu g/kg, i.p.), LPS-evoked TNF-alpha in maternal serum and amniotic fluid was significantly inhibited. Importantly, low-dose LPS pretreatment also greatly attenuated LPS-induced increases in TNF-alpha protein in fetal liver and fetal brain. Taken together, these results indicate that perinatal exposure to low-dose LPS induces a reduced sensitivity to subsequent LPS challenge. (c) 2007 Published by Elsevier Ireland Ltd.