de Groot M J, van Helden M A, de Jong Y F, Coumans W A, van der Vusse G J
Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
Mol Cell Biochem. 1995 May 24;146(2):147-55. doi: 10.1007/BF00944607.
Previous studies have shown that exogenous lactate impairs mechanical function of reperfused ischaemic hearts, while pyruvate improves post-ischaemic recovery. The aim of this study was to investigate whether the diverging influence of exogenous lactate and pyruvate on functional recovery can be explained by an effect of the exogenous substrates on endogenous protecting mechanisms against oxygen-derived free radicals. Isolated working rat hearts were perfused by a Krebs-Henseleit bicarbonate buffer containing glucose (5 mM) as basal substrate and either lactate (5 mM) or pyruvate (5 mM) as cosubstrate. In hearts perfused with glucose as sole substrate the activity of glutathione reductase was decreased by 32% during 30 min of ischaemia (p < 0.10 versus control value), while the activity of superoxide dismutase and catalase was reduced by 27 and 35%, respectively, during 5 min of reperfusion (p < 0.10 versus control value). The GSH level in the glucose group was reduced by 29% following 30 min of ischaemia and 35 min of reperfusion (p < 0.10). In lactate- and pyruvateperfused hearts there were no significant decreases of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activity during 30 min of ischaemia, 5 min of reperfusion or 35 min of reperfusion. In pyruvate-perfused hearts the glutathione peroxidase activity was even increased by 43% during 30 min of ischaemia (p < 0.05). Glutathione levels (reduced and oxidized) did not markedly change in the lactate and pyruvate groups.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，外源性乳酸会损害再灌注缺血心脏的机械功能，而丙酮酸可改善缺血后的恢复。本研究的目的是调查外源性乳酸和丙酮酸对功能恢复的不同影响是否可以通过外源性底物对内源性抗氧自由基保护机制的作用来解释。将离体工作的大鼠心脏用含有葡萄糖（5 mM）作为基础底物以及乳酸（5 mM）或丙酮酸（5 mM）作为共底物的 Krebs-Henseleit 碳酸氢盐缓冲液灌注。在以葡萄糖作为唯一底物灌注的心脏中，缺血30分钟期间谷胱甘肽还原酶的活性降低了32%（与对照值相比，p < 0.10），而在再灌注5分钟期间超氧化物歧化酶和过氧化氢酶的活性分别降低了27%和35%（与对照值相比，p < 0.10）。缺血30分钟和再灌注35分钟后，葡萄糖组的谷胱甘肽水平降低了29%（p < 0.10）。在灌注乳酸和丙酮酸的心脏中，缺血30分钟、再灌注5分钟或再灌注35分钟期间，超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性均无显著降低。在灌注丙酮酸的心脏中，缺血30分钟期间谷胱甘肽过氧化物酶的活性甚至增加了43%（p < 0.05）。乳酸和丙酮酸组的谷胱甘肽水平（还原型和氧化型）没有明显变化。（摘要截短至250字）
