Oxygen radical injury and loss of high-energy compounds in anoxic and reperfused rat heart: prevention by exogenous fructose-1,6-bisphosphate.
Oxygen radical injury and loss of high-energy compounds in anoxic and reperfused rat heart: prevention by exogenous fructose-1,6-bisphosphate.
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缺氧和再灌注大鼠心脏中的氧自由基损伤和高能化合物损失：外源性果糖-1,6-二磷酸的预防。
DOI：
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Bruno Giardina
中科院分区：
文献类型：
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作者：
B. Tavazzi;Loredana Cerroni;D. Pierro;G. Lazzarino;Matti Nuutinen;Joseph W. Starnes;Bruno Giardina
离体Langendorff灌注大鼠心脏在10分钟预灌注后，进行无底物缺氧灌注（20分钟），随后用含葡萄糖的氧平衡培养基再灌注20分钟。在相同的灌流条件下，研究了外源性5 mM果糖-1，6-二磷酸的作用。黄嘌呤脱氢酶黄嘌呤氧化酶的比例，高能量磷酸盐和TBA反应性物质（TBARS）的浓度进行了测定，在每个灌注期结束时，在控制和果糖-1，6-二磷酸治疗的心脏。结果表明，缺氧引起心肌能量代谢急剧下降，导致黄嘌呤脱氢酶不可逆地转化为氧化酶。这一发现得到了外源性果糖-1，6-二磷酸的保护作用的支持，外源性果糖-1，6-二磷酸能够通过防止缺氧期间磷酸化化合物的耗尽来维持正确的黄嘌呤脱氢酶/氧化酶比率。此外，在对照心脏中，再灌注期间乳酸脱氢酶的释放被组织TBARS浓度增加50%所抑制。相反，在果糖-1，6-二磷酸处理的心脏中，该浓度在复氧后没有显著变化，而观察到灌注液中乳酸脱氢酶活性轻微但显著增加。总的来说，这些数据表明氧自由基对缺氧后心脏恶化的直接贡献。本文提出了1，6-二磷酸果糖在缺氧再灌注大鼠心脏中的作用机制及其在心肌梗塞临床治疗中的可能应用。
Isolated Langendorff-perfused rat hearts after 10 minutes preperfusion, were subjected to a substrate-free anoxic perfusion (20 minutes) followed by 20 minutes reperfusion with a glucose-containing oxygen-balanced medium. Under the same perfusion conditions, the effect of exogenous 5mM fructose-1,6-bisphosphate has been investigated. The xanthine dehydrogenase to xanthine oxidase ratio, concentrations of high-energy phosphates and of TBA-reactive material (TBARS) were determined at the end of each perfusion period in both control and fructose-1,6-bisphosphate-treated hearts. Results indicate that anoxia induces the irreversible transformation of xanthine dehydrogenase into oxidase as a consequence of the sharp decrease of the myocardial energy metabolism. This finding is supported by the protective effect exerted by exogenous fructose-1,6-bisphosphate which is able to maintain the correct xanthine dehydrogenase/oxidase ratio by preventing the depletion of phosphorylated compounds during anoxia. Moreover, in control hearts, the release of lactate dehydrogenase during reperfusion, is paralleled by a 50% increase in the concentration of tissue TBARS. On the contrary, in fructose-1,6-bisphosphate-treated hearts this concentration does not significantly change after reoxygenation, while a slight but significant increase of lactate dehydrogenase activity in the perfusates is observed. On the whole these data indicate a direct contribution of oxygen-derived free radicals to the worsening of post-anoxic hearts. A hypothesis on the mechanism of action of fructose-1,6-bisphosphate in anoxic and reperfused rat heart and its possible application in the clinical therapy of myocardial infarction are presented.
DOI：
10.1073/pnas.85.11.4046
发表时间：
1988-06-01
影响因子：
11.1
作者：
ZWEIER, JL;KUPPUSAMY, P;LUTTY, GA
通讯作者：
LUTTY, GA