2004.3,.29【英译中】妊娠糖尿病诱发慢性缺氧应激和小鼠胎盘过度炎症反应【4】

一只筱蝶 (一只筱蝶) 路人甲
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发表于:2014-03-29 17:03 [只看楼主] [划词开启]

To further elucidate the mechanisms that a heavy function burden in HF group leads to preeclampsia, fetal growth restriction, infant death, stillbirth and other complications, the key finding in these studies was that GDM results in increased placental oxidative stress, as the most frequently used indicators of lipid peroxidation and biomarker of oxidative stress, MDA level in HF placenta was increased by 84.4 % over in whole placental homogenates of GD18.5.

为了进一步阐明,HF组沉重功能负担导致子痫前期,胎儿生长受限,婴儿死亡,死胎等并发症的机制,这些研究中的关键发现是GDM增加了胎盘的氧化应激,作为最常用的脂质过氧化和氧化应激生物标志物的指标,在HF组,妊娠第18.5天,胎盘MDA水平在整个胎盘匀浆中增加了84.4 %。


 At the first trimester, excessive production of reactive oxygen species may break the balance of hypoxia-reoxygenation on trophoblast development such as invading shallowly; and in late gestation, hypoxia has been shown to cause apoptosis of trophoblast and vascular endothelium cells, which changes were all observed in preeclampsia, These may explains why GDM has a high incidence of preeclampsia .

The primary molecular sensor used by trophoblasts and the developing embryo to sense and respond to changes in O2 tension is HIF-1α . Through transcriptional activation the HIF-1α regulates many different cellular processes in response to hypoxia, including angiogenesis. In human placenta, Myatt et al suggested that oxidative stress may cause vascular dysfunction in the placenta that compromises fetal growth

  在孕早期,过度产生的活性氧可能打破滋养层发育缺氧复氧平衡,比如浅侵入。在孕后期,缺氧已被证明是导致滋养细胞和血管内皮细胞凋亡的原因,在子痫前期观察到这些变化。这也许解释了为什么妊娠期糖尿病先兆子痫的发病率增加。滋养细胞和发育中的胚胎以感知和响应O2张力变化的主要分子传感器是HIF-1α。通过转录激活的HIF-1α的调节响应不同的细胞过程对缺氧的反应,包括血管生成。在人类胎盘,Myatt等认为氧化应激可导致胎盘血管功能障碍,损害胎儿生长。


The higher level of HIF-1α expression showed a lower O2 tension. Our results proved that HF induced HIF-1α not only in mRNA level but also in protein level. HIF-1α and low O2 tension are important in early pregnant, including regulation of angiogenesis, migration/invasion and cell metabolism, but in late placenta, it seems not so good for pregnancy. Our findings suggested that HF had a confused and disordered vascular structure. Pietro et al indicated that the change in the placental VEGF/VEGFR expression ratio in mild hyperglycemia may favor angiogenesis in placental tissue.

    HIF-1α表达水平升高,氧张力降低。我们的研究结果证明,HF不仅在mRNA水平,而且在蛋白水平诱导HIF-1α。早孕期,HIF-1α和低氧张力很重要,包括血管生成,迁移/侵袭和细胞代谢的调控,但在孕后期的胎盘,似乎这些对怀孕没有那么好。我们的研究结果表明,HF组有混乱无序的血管结构。Pietro等指出,轻度高血糖的胎盘VEGF/VEGFR表达比的变化可能有利于胎盘组织中的血管生成。


  In our studies, the increase of VEGF level might be also induced by HIF-1α in HF group. However, we also found that CD31 staining intensity in placenta of HF group is not inconsistent with the increase degree of HIF-1α and VEGF, which suggested that angiogenesis in HF placenta may be not enough, although the level of angiogenesis related factors, such as VEGF, IL-6, was significantly increased. These results are partly echoed with Liang et al. VEGF levels highly increased in human late gestational placenta, but vascular structure was not growing because one of VEGF receptor FLT-1 in placenta was decreased, but soluble FLT-1 (sFLT-1) expression in a free serum could combine with VEGF, which could not ensure the neoformation of placental vessels and their organization to meet the needs of the fetus and placentas.

在我们的研究中,血管内皮生长因子水平的增加可能也是HF组诱发HIF-1α的原因。然而,我们也发现,在HF组胎盘CD31染色强度是不符合HIF-1α和血管内皮生长因子增加程度的,提示HF组胎盘血管生成可能是不够的,虽然血管生成相关的因素,如血管内皮生长因子,IL-6水平显著增加。这些结果与Liang等人的研究有部分重叠。VEGF水平在人类妊娠晚期胎盘大量增加,但血管结构不发展是因为血管内皮生长因子受体FLT-1在胎盘降低,但可溶性FLT-1SFLT-1)在无血清的表达能结合VEGF,因此不能确保胎盘血管的新生物和其组织能满足胎儿和胎盘的需要。


Our results also showed that GDM and obesity placentas could not have an adaptive capacity, besides impaired angiogenesis Radaelli et al  showed placental transcriptome emerged as a primary target of the altered environment of diabetic pregnancy. The genes identified provide the basis to elucidate links between inflammatory pathways and GDM-associated insulin resistance. Desoye et showed a similar results with Radaelli’s that GDM induced a significantly increase in IL-6 mRNA levels in GDM placenta, there were no major differences in immune cell populations within the placental villi and only a greater degree of muscularity in the vessel walls. Zhou et al  showed that increased TNF-α/IL-6 signaling in mice was a key mechanism underlying increased preeclampsia, and IL-6 blockade inhibited preeclamptic features in autoantibody-injected pregnant mice. In our studies, it could be observed that an exaggerated inflammation response in HF placentas. Because these factors and biological behaviors were closely related with each other, when the balance in placenta disturbed, such as misbalance of endothelial hypoxia, proliferation and apoptosis behaviors, which may contribute to a high risk of complications.

我们的结果还表明,妊娠期糖尿病和肥胖的胎盘不可能有适应能力,除了受损血管生成,Radaelli等人发现胎盘转录成为改变妊娠期糖尿病环境的一个主要目标。被识别的基因,为阐明炎症通路和GDM相关的胰岛素抵抗之间的联系提供了基础。Desoye等人提出与Radaelli类似的研究结果。GDM诱导的IL-6mRNA水平在妊娠期糖尿病胎盘显著增加,在胎盘绒毛及更大的血管壁内免疫细胞群没有大的差异。Zhou等的研究表明增加TNF-α/IL-6信号是大鼠先兆子痫增加的关键机制,孕鼠注射抗体IL-6,可抑制先兆子痫的发生。在我们的研究中,可以观察到, HF组胎盘过度炎症反应。由于这些因素和生物学行为密切相关,当胎盘的平衡受到干扰,如内皮细胞缺氧,细胞增殖和凋亡,这可能会导致并发症的高风险。

最后编辑于:2014-03-29 17:05
分类: 英语

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