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首页> 外文期刊>American Journal of Physiology >Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia.
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Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia.

机译：作为适应体内慢性缺氧的标志物，更大的血管，降低的HIF-1 / DNA结合以及升高的GSH。

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Vascularity is increased in placentas from high- compared with low-altitude pregnancies. An angiogenic response to hypoxia may protect an organ from further hypoxic insult by increasing blood flow and oxygen delivery to the tissue. We hypothesized that increased placental vascularity is sufficient to adapt to high altitude. Therefore, indexes of hypoxic stress would not be present in placentas from successful high-altitude pregnancies. Full-thickness placental biopsies were 1) collected and frozen in liquid nitrogen within 5 min of placental delivery and 2) fixed in formalin for stereologic analyses at high (3,100 m, n = 10) and low (1,600 m, n = 10) altitude. Hypoxia-inducible transcription factor (HIF-1) activity was analyzed by ELISA. Western blot analyses were used to evaluate HIF-1alpha, HIF-1beta, HIF-2alpha, von Hippel-Lindau protein, VEGF, Flt-1, enolase, and GAPDH. Magnetic resonance spectroscopy was used to evaluate endogenous metabolism. The ratio of placental capillary surface density to villous surface density was 70% greater at high compared with low altitude. HIF-1 activity and HIF-1-associated proteins were unchanged in placentas from high- vs. low-altitude pregnancies. Placental expression of HIF-1-mediated proteins VEGF, Flt-1, enolase, and GAPDH were unchanged at high vs. low altitude. Succinate, GSH, phosphomonoesters, and ADP were elevated in placenta from high compared with low altitude. Placentas from uncomplicated high-altitude pregnancies have greater vascularity and no indication of significant hypoxic stress at term compared with placentas from low altitude.
机译：高海拔孕妇与低海拔孕妇相比，胎盘血管增加。对缺氧的血管生成反应可通过增加血流量和向组织的氧输送来保护器官免受进一步的低氧损伤。我们假设胎盘血管的增加足以适应高原。因此，成功进行高海拔妊娠的胎盘中不会出现低氧应激指数。采集全厚度的胎盘活检组织1）在胎盘娩出后5分钟内将其冷冻并在液氮中冷冻; 2）在高海拔（3,100 m，n = 10）和低海拔（1,600 m，n = 10）的情况下固定在福尔马林中进行立体分析。通过ELISA分析低氧诱导的转录因子（HIF-1）活性。蛋白质印迹分析用于评估HIF-1alpha，HIF-1beta，HIF-2alpha，von Hippel-Lindau蛋白，VEGF，Flt-1，烯醇酶和GAPDH。磁共振波谱用于评估内源性代谢。高海拔时胎盘毛细血管表面密度与绒毛表面密度之比比低海拔高70％。高海拔孕妇和低海拔孕妇的胎盘中HIF-1活性和HIF-1相关蛋白均未改变。 HIF-1介导的蛋白VEGF，Flt-1，烯醇酶和GAPDH的胎盘表达在高海拔和低海拔都没有变化。与高海拔相比，琥珀酸，谷胱甘肽，磷酸单酯和ADP在胎盘中从高处升高。与来自低海拔地区的胎盘相比，来自单纯性高海拔妊娠的胎盘具有更大的血管性，并且在足月时没有明显的低氧应激迹象。

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