Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver.

Evidence that hypoxia markers detect oxygen gradients in liver: pimonidazole and retrograde perfusion of rat liver.
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DOI:
10.1038/bjc.1995.429
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发表时间:
1995-10
影响因子:
8.8
通讯作者:
Raleigh JA
Raleigh JA
中科院分区:
医学1区
文献类型:
--
作者:
Arteel GE;Thurman RG;Yates JM;Raleigh JA

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肿瘤缺氧的硝基咪唑标记物与含氧量正常的肝脏结合,这是否是由于低氧浓度或专门的硝基还原酶的微区域活性引起的问题已经提出。为了回答这个问题,结合模式的2-硝基咪唑,pimonidazole,进行了比较灌注手术分离的大鼠肝脏在顺行和逆行方向。在顺行或逆行方向上以低流速灌注可以有意地用于改变氧梯度而不改变酶分布。灌注通过门静脉(顺行方向)产生的匹莫硝唑结合在肝的中央周围区域类似于观察到的匹莫硝唑结合在体内。当通过中央静脉(逆行方向)灌注离体肝脏时,这种结合模式发生完全逆转。在这种情况下,匹莫硝唑结合发生在门静脉周围区域。在逆行灌注期间门静脉周围区域的结合程度和强度与顺行灌注期间中央周围区域的结合程度和强度相似。得出结论,低氧浓度,而不是硝基还原酶活性的非均匀分布是2-硝基咪唑结合在肝脏中的主要决定因素。
Nitroimidazole markers of tumour hypoxia bind to normoxic liver and the question has been raised whether this is due to low oxygen concentration or microregional activity of specialised nitroreductases. To answer this question, the binding patterns of the 2-nitroimidazole, pimonidazole, were compared following perfusion of surgically isolated rat livers in anterograde and retrograde directions. Perfusion at low flow rates in anterograde or retrograde directions can be used intentionally to alter oxygen gradients without altering enzyme distributions. Perfusion by means of the portal vein (anterograde direction) produced pimonidazole binding in the pericentral region of liver similar to that observed for pimonidazole binding in vivo. A complete reversal of this binding pattern occurred when the isolated liver was perfused by way of the central vein (retrograde direction). In this case, pimonidazole binding occurred in the periportal region. The extent and intensity of binding in the periportal region during perfusion in the retrograde direction was similar to that in the pericentral region during perfusion in the anterograde direction. It is concluded that low oxygen concentration rather than the non-homogeneous distribution of nitroreductase activity is the primary determinant of 2-nitroimidazole binding in liver.
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