Nguyen M V C, Pouvreau S, El Hajjaji F Z, Denavit-Saubie M, Pequignot J M
CNRS UPR 2216, Neurobiologie Génétique et Intégrative, Institut Alfred Fessard, Gif/Yvette, France.
J Neurosci Res. 2007 Apr;85(5):1119-25. doi: 10.1002/jnr.21202.
The iron chelator desferrioxamine (DFO) induces accumulation of the hypoxia-inducible factor (HIF-1), a transcription factor that up-regulates genes involved in adaptative responses to hypoxia. This property makes DFO a potential neuroprotector against hypoxic stress. We investigated in rats the effects of DFO on the ventilatory response to mild hypoxic tests and the expression of tyrosine hydroxylase (TH), a target gene of HIF-1. Two protocols were used, the first with repeated injections of 50 mg/kg DFO every 2 days during a 2-week period. This was aimed at define the time course of the ventilatory responses to a hypoxic test. In the second protocol, rats were given a single injection of 300 mg/kg DFO. Every day over 4 days, the hypoxic ventilatory response was recorded before the animal was sacrificed, and Western blot analysis of TH in the dorsal brainstem cardiorespiratory area was performed. DFO produced a delayed increase in the hypoxic ventilatory response, which appeared in the same time window as TH up-regulation (2-3 days after the bolus injection of DFO). This delay suggests a genic effect of the drug that improves the ventilatory response to hypoxia.
铁螯合剂去铁胺（DFO）可诱导缺氧诱导因子（HIF-1）的积累，HIF-1是一种转录因子，可上调参与缺氧适应性反应的基因。这一特性使DFO成为一种潜在的抗缺氧应激神经保护剂。我们在大鼠中研究了DFO对轻度缺氧试验通气反应以及HIF-1靶基因酪氨酸羟化酶（TH）表达的影响。采用了两种方案，第一种方案是在2周内每2天重复注射50mg/kg DFO。这旨在确定对缺氧试验通气反应的时间进程。在第二种方案中，给大鼠单次注射300mg/kg DFO。在4天的时间里，每天在处死动物前记录缺氧通气反应，并对延髓背侧心肺区域的TH进行蛋白质印迹分析。DFO使缺氧通气反应延迟增加，这与TH上调出现在同一时间窗内（DFO单次推注后2 - 3天）。这种延迟表明该药物具有基因效应，可改善对缺氧的通气反应。
