Treatment of Lipoxin A4 and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms
Treatment of Lipoxin A4 and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms
复制标题
脂氧素A(4)及其类似物对低剂量内毒素诱导的大鼠先兆子痫的治疗作用及其可能机制。
DOI：
10.1016/j.reprotox.2012.09.009
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发表时间：
2012-12-01
影响因子：
3.3
通讯作者：
Huang, Yinping
中科院分区：
文献类型：
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作者：
Lin, Feng;Zeng, Pan;Huang, Yinping
已知先兆子痫 (PE) 代表母体对妊娠的过度炎症反应。脂氧素 A(4) (LXA(4)) 被认为是炎症中的内源性停止信号，因其炎症促消退作用已在临床前进行了广泛研究。因此，在本研究中，我们测试了BML-111（LXA（4）的合成类似物）对低剂量内毒素（LPS）诱导的实验性PE大鼠的作用以及LXA（4）对人绒毛外滋养层细胞系（TEV-1）的作用。体内实验结果表明，BML-111可有效缓解收缩压、24小时尿白蛋白排泄量、血清TNF-α和IL-8水平以及LPS引起的胎盘和肾脏形态损伤。 LXA(4) 还抑制 LPS 触发的细胞凋亡、TEV-1 细胞中 NF-κ B、TNF-α 和 IL-8 mRNA 和蛋白表达的激活。同时，BML-111 保护细胞免受 LPS 抑制的增殖。目前的研究首次证明LXA(4)可以缓解内毒素暴露大鼠的PE症状。 (C) 2012 Elsevier Inc. 保留所有权利。
Preeclampsia (PE) is known to represent an exaggerated maternal inflammatory response to pregnancy. Lipoxin A(4) (LXA(4)), considered as an endogenous stop signal in inflammation, has been extensively studied pre clinically for its inflammatory pro-resolving effects. Thus, in the current study, we tested the effect of BML-111 (synthetic analogue of LXA(4)) on experimental PE rats induced by low-dose endotoxin (LPS) and of LXA(4) on human extravillous trophoblast cell line (TEV-1). In vivo experiment results showed that systolic blood pressure, 24 h-urinary albumin excretion, serum TNF-alpha and IL-8 levels and morphologic damage of placenta and kidney caused by LPS were all effectively alleviated by BML-111. LXA(4) also inhibited LPS-triggered apoptosis, activation of NF-kappa B, TNF-alpha and IL-8 mRNA and protein expression in TEV-1 cells. At the same time, BML-111 protected the cells from LPS-reduced proliferation. The current study demonstrated for the first time that LXA(4) could alleviate the symptoms of PE in endotoxin exposed rats. (C) 2012 Elsevier Inc. All rights reserved.