Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta
Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta
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DOI：
10.1016/j.placenta.2004.05.004
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发表时间：
2005-02-01
期刊：
影响因子：
3.8
通讯作者：
Wang, Y
中科院分区：
文献类型：
--
作者：
Li, H;Gu, B;Wang, Y
目的：胎盘滋养层细胞（TC）分泌可溶性Flt-1（sFIt-1）。缺氧诱导胎盘氧化应激并调节滋养层功能。本研究的目的是探讨是否缺氧介导TC sFlt-1的生产和是否增加sFlt-1生产与增加氧化应激在胎盘TCs.Methods：胎盘分娩后立即从正常孕妇（n = 8）。通过Dispase消化绒毛组织分离胎盘TC，并通过Percoll梯度离心纯化。将分离的TC在常氧（21%O-2：5%CO2/95%空气）和缺氧（2%O-2/5%CO2/93%N2）条件下体外培养3天。酶联免疫吸附试验（ELISA）检测TC对sFlt-1、VEGF和PIGF的表达。脂质过氧化物的产生和超氧化物歧化酶（CuZn-SOD）水平进行了评价。RT-PCR检测Flt-1、VEGF和PIGF mRNA的表达。超氧化物歧化酶（CuZn-SOD）和血红素加氧酶-1（HO-1）的信使RNA表达也进行了测定。数据表示为平均值+/- SE。p水平小于0.05被认为是statistically different.Results：我们的研究结果表明，sFlt-1的生产显着增加T TC在缺氧条件下培养，与脂质过氧化物的生产增加。我们还发现，在缺氧条件下。结果表明：（1）PlGF/VEGF比值逆转，（2）脂质过氧化物/超氧化物歧化酶比值升高。胎盘TC中Flt-1和VEGF mRNA表达的增加和PlGF mRNA表达的减少与缺氧条件下的蛋白质产生一致。结论：胎盘TC中sFlt-1的上调和PlGF/VEGF的不平衡产生与氧化应激增加有关，是缺氧的后果。我们的研究结果表明，胎盘TC的sFlt-1和VEGF水平的主要来源，在母体循环中先兆子痫的妇女。
Objective: Placental trophoblast cells (TCs) produce soluble Flt-1 (sFIt-1). Hypoxia induces placental oxidative stress and modulates trophoblast function. The aim of this study was to investigate whether hypoxia mediates TC sFlt-1 production and whether increased sFlt-1 production correlates with increased oxidative stress in placental TCs.Methods: Placentas were obtained immediately after delivery from normal pregnant women (n = 8). Placental TCs were isolated by Dispase digestion of villous tissue and purified by Percoll gradient centrifugation. Isolated TCs were cultured under normoxia (21% O-2: 5% CO2/95% air) and hypoxia (2% O-2/5 % CO2/93% N2) conditions for 3 days in vitro. TC productions of sFlt-1, VEGF, and PIGF were measured bv enzyme-linked immunosorbent assay (ELISA). Lipid peroxide production and superoxide dismutase (CuZn-SOD) levels were evaluated. Messenger RNA expressions of Flt-1, VEGF and PIGF were determined by RT-PCR. Messenger RNA expressions for superoxide dismutase (CuZn-SOD) and heme oxygenase-1 (HO-1) were also determined. Data are expressed as mean +/- SE. A p level less than 0.05 was considered statistically different.Results: Our results show that sFlt-1 production was significantly increased by T TCs cultured under hypoxia condition that correlates with increased lipid peroxide production. We also found that under hypoxia. condition: (1) the ratio of PlGF/VEGF production was reversed; (2) the ratio of lipid peroxides to superoxide dismutase production was increased. The increased mRNA expressions for Flt-1 and VEGF and the decreased mRNA expression for PlGF in TCs were consistent with the protein productions under hypoxia condition.Conclusion: We concluded that upregulation of sFlt-1 and unbalanced PlGF/VEGF production associated with increased oxidative stress are consequences of hypoxia in placental TCs. Our results suggest that placental TCs are major sources of sFlt-1 and VEGF levels in the maternal circulation in women with preeclampsia.