Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts.
Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts.
复制标题
缺血再灌注大鼠心脏膜磷脂降解机制。
DOI：
10.1152/ajpheart.1989.257.1.h252
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Das,DK
中科院分区：
文献类型：
--
作者：
Otani,H;Prasad,MR;Jones,RM;Das,DK
本实验采用离体大鼠心脏灌流模型，研究了缺血心肌再灌注过程中膜磷脂降解的机制。常温下全脑缺血30分钟后再灌注30分钟，导致磷脂酰胆碱（PC）含量显著降低，溶血磷脂酰胆碱（LPC）含量显著增加。心肌缺血长达60分钟没有造成任何主要磷脂的显着损失。与正常灌注心脏相比，缺血再灌注心脏中[14 C]花生四烯酸（AA）和[3 H]-甘油与PC的同位素结合显著减弱，表明再灌注期间PC合成的再酰化和从头途径均被灭活。在[14 C]AA预标记的心脏中，放射性标记的PC在再灌注期间显著降低，与[14 C]AA累积的小但显著的增加相关。再灌注过程中PC含量和[14 C]AA掺入PC的减少，以及LPC含量和[14 C]AA的增加，可通过低Ca 2+（50 μ M）缓冲液再灌注或用三氟拉嗪（10 μ M）或米帕林（50 μ M）预处理来阻止，但维拉帕米（1 μ M）不能阻止。PC丢失的抑制与再灌注心脏肌酸激酶释放的显着减少有关。目前的研究表明，膜磷脂的净损失，特别是相对于PC在再灌注期间，可能导致1）抑制AA的再酰化，2）抑制从头合成，和3）刺激磷脂酶活性。这些结果与Ca 2+的流入一致，尽管其他解释也是可能的。
We investigated the mechanism of membrane phospholipid degradation during reperfusion of ischemic myocardium using isolated and perfused rat hearts. Thirty min of myocardial reperfusion after 30 min of normothermic global ischemia resulted in a significant decrease of phosphatidylcholine (PC) content associated with a small but significant increase in lysophosphatidylcholine (LPC) content. Myocardial ischemia for up to 60 min caused no significant loss of any of the major phospholipids. Isotopic incorporation of [14C]arachidonic acid (AA) as well as [3H]-glycerol into PC was significantly attenuated in the ischemic-reperfused heart compared with the normally perfused heart, suggesting that both reacylation and de novo pathways for PC synthesis were inactivated during reperfusion. In the heart prelabeled with [14C]AA, the radiolabeled PC was decreased significantly during reperfusion, associated with a small but significant increase in [14C]AA accumulation. The decreases of PC content and incorporation of [14C]AA into PC, as well as the increases of LPC content and the [14C]AA during reperfusion, were prevented by reperfusion with low Ca2+ (50 microM) buffer or by pretreatment with trifluoperazine (10 microM) or mepacrine (50 microM), but not with verapamil (1 microM). The inhibition of loss of PC was associated with significant diminution of creatine kinase release from the reperfused hearts. The present study indicates that the net loss of membrane phospholipids, especially with respect to PC during reperfusion, may result from 1) inhibition of reacylation of AA, 2) inhibition of de novo synthesis, and 3) stimulation of phospholipase activity. These results are consistent with an influx of Ca2+, although other interpretations are also possible.