Response of purine metabolism and cortical oxygen pressure to hypoxia and reoxygenation in newborn piglets.

Response of purine metabolism and cortical oxygen pressure to hypoxia and reoxygenation in newborn piglets.
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新生仔猪嘌呤代谢和皮质氧压对缺氧和复氧的反应。

DOI:
10.1007/978-1-4615-5399-1_21
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发表时间:
1997
影响因子:
--
通讯作者:
Wilson,DF
Wilson,DF
中科院分区:
医学4区
文献类型:
--
作者:
Pastuszko,P;Marro,P;Delivoria-Papadopoulos,M;Wilson,DF

文献摘要

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有人提出,嘌呤代谢物(特别是次黄嘌呤)的水平反映了细胞内的能量代谢,可以作为组织对缺氧/缺血条件反应的敏感、特异性标志物。26,27多项研究表明,缺氧条件会导致细胞核苷酸分解,导致次黄嘌呤和黄嘌呤的积累4,7,8,28,这些代谢物可以作为可氧化的嘌呤底物用于黄嘌呤脱氢酶和氧化酶。缺氧/缺血条件下复氧过程中组织损伤的可能机制之一是次黄嘌呤-黄嘌呤氧化酶反应产生自由基。1,5,615,16,24,29在缺氧/缺血条件下,胞质钙浓度升高可以激活蛋白酶钙蛋白酶,将黄嘌呤脱氢酶转化为黄嘌呤氧化酶。32 在缺氧后复氧过程中,黄嘌呤氧化酶催化黄嘌呤氧化为尿酸,并形成超氧自由基 O24,15,28。超氧自由基可以进一步与同一反应中产生的过氧化氢反应,形成羟基自由基。黄嘌呤氧化酶的有毒氧代谢物对复氧过程中组织损伤的贡献主要基于研究表明黄嘌呤氧化酶抑制剂(例如别嘌呤醇)可减少不同组织的缺血后损伤。9,19,20,21,24
It has been proposed that the level of purine metabolites (particularly hypoxanthine) reflects the intracellular energy metabolism and can be used as sensitive, specific markers of response of tissue to hypoxic/ischemic conditions.26,27Several studies have shown that hypoxic conditions cause breakdown of cellular nucleotides resulting in accumulation of hypoxanthine and xanthine4,7,8,28and these metabolites can serve as oxidizable purine sub-strates for xanthine dehydrogenase and oxidase. One of the possible mechanisms of tissue damage during reoxygenation following hypoxic/ischemic conditions is through genera-tion of free radicals by the hypoxanthine-xanthine oxidase reactions.1,5,615,16,24,29Under hy-poxic/ischemic conditions the elevated cytosolic calcium concentration can activate a protease, calpain, which converts xanthine dehydrogenase to xanthine oxidase.32During posthypoxic reoxygenation xanthine oxidase catalyzes oxidation of xanthine to uric acid with formation of Superoxide radical O24,15,28. The Superoxide radical can further react with hydrogen peroxide produced in the same reaction and form hydroxyl radicals. Contribution of toxic oxygen metabolites from xanthine oxidase to tissue injury during reoxy-genation has been based particularly on studies showing that the inhibitors of xanthine oxidase, such as allopurinol, decrease the postischemic injury of different tissues.9,19,20,21,24