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用百草枯灌注大鼠肺时葡萄糖代谢的变化。

Alterations of glucose metabolism during perfusion of rat lung with paraquat.

作者信息

Bassett D J, Fisher A B

出版信息

Am J Physiol. 1978 Jun;234(6):E653-9. doi: 10.1152/ajpendo.1978.234.6.E653.

DOI:10.1152/ajpendo.1978.234.6.E653
PMID:27101
Abstract

Isolated perfused rat lungs were used to investigate effects of paraquat on lung glucose metabolism. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate buffer, pH 7.4, containing albumin and 5.5 mM radiolabeled D-glucose. Control lung glucose utilization, estimated from rate of 3H2O production from [5-3H]glucose, was 44 mumol/h-g dry wt. Pentose cycle activity, based on 14CO2 specific yields at the end of perfusions with [1-14C]- and [6-14C]glucose, was 14% of glucose utilization. During perfusion with 1.5 mM paraquat, glucose utilization increased 28%, 14CO2 production via the pentose cycle increased 182% (P less than 0.005), CO2 production via mitochondrial metabolism increased 39% (P less than 0.02), and the rate of lactate production increased 28% (P less than 0.05). Pyruvate production and the lactate-to-pyruvate ratio were not significantly altered. The data indicate that interaction of paraquat with the lung results in increased turnover of cytoplasmic NADPH and increased mitochondrial metabolism, but no significant change in cytoplasmic redox state. The findings are compatible with intracellular enzymatic reduction of paraquat by an NADPH-requiring reductase.

摘要

采用离体灌注大鼠肺脏来研究百草枯对肺脏葡萄糖代谢的影响。肺脏用含5%二氧化碳的空气进行通气,并灌注pH 7.4的 Krebs-Ringer碳酸氢盐缓冲液,其中含有白蛋白和5.5 mM放射性标记的D-葡萄糖。根据[5-³H]葡萄糖产生³H₂O的速率估算,对照肺脏的葡萄糖利用率为44 μmol/h-g干重。根据用[1-¹⁴C]-和[6-¹⁴C]葡萄糖灌注结束时¹⁴CO₂的特定产量计算,戊糖循环活性为葡萄糖利用率的14%。在用1.5 mM百草枯灌注期间,葡萄糖利用率增加了28%,通过戊糖循环的¹⁴CO₂产生增加了182%(P<0.005),通过线粒体代谢的CO₂产生增加了39%(P<0.02),乳酸产生速率增加了28%(P<0.05)。丙酮酸产生和乳酸与丙酮酸的比率没有显著改变。数据表明,百草枯与肺脏的相互作用导致细胞质NADPH周转增加和线粒体代谢增加,但细胞质氧化还原状态没有显著变化。这些发现与需要NADPH的还原酶对百草枯进行细胞内酶促还原相一致。

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