Flynn J T
Prostaglandins Leukot Med. 1987 May;27(2-3):93-103. doi: 10.1016/0262-1746(87)90063-1.
Activated components of the complement system have been shown to stimulate the arachidonic acid cascade. We have reported that hepatic thromboxane production in response to plasma activated with zymosan is self-limiting, not affected by nifedipine, but inhibited by mepacrine, a phospholipase inhibitor. To further study this relationship, we have tested the effects of dantrolene sodium, an agent reported to immobilize intracellular calcium. Control group livers were perfused with Krebs-Henseleit bicarbonate buffer at a rate of 120 ml/min in a nonrecirculating perfusion system and administered 1 ml/min of normal rabbit plasma for 10 minutes. This group of livers demonstrated stable wet weight, perfusion pressure, and rates of release of lactic dehydrogenase, thromboxane B2, and prostacyclin over a 150 minute experimental period. In contrast, the administration of 1 ml/min of zymosan-activated plasma resulted in significant increases in the rate of thromboxane B2 release at 1, 3, and 5 minutes after the start of the infusion. The rate of thromboxane production then returned to baseline values. Neither prostacyclin nor lactic dehydrogenase release changed significantly after ZAP. A similar change in thromboxane production following ZAP administration was seen in livers being continually perfused with 10 microM dantrolene sodium. Perfusion pressure was significantly elevated in this group during the ZAP infusion period. These results confirm complement-mediated thromboxane production in the isolated rabbit liver model but do not describe a definitive role of dantrolene-sensitive intracellular calcium release in the mechanism of ZAP-mediated thromboxane production.
补体系统的活化成分已被证明能刺激花生四烯酸级联反应。我们曾报道，酵母聚糖激活血浆后肝脏血栓素的产生是自我限制的，不受硝苯地平影响，但受磷脂酶抑制剂米帕林抑制。为进一步研究这种关系，我们测试了丹曲林钠的作用，据报道该药物能固定细胞内钙。在非循环灌注系统中，对照组肝脏以120毫升/分钟的速度用Krebs-Henseleit碳酸氢盐缓冲液灌注，并在10分钟内以1毫升/分钟的速度给予正常兔血浆。在150分钟的实验期内，该组肝脏的湿重、灌注压力以及乳酸脱氢酶、血栓素B2和前列环素的释放率保持稳定。相比之下，以1毫升/分钟的速度给予酵母聚糖激活血浆后，在输注开始后的1、3和5分钟，血栓素B2的释放率显著增加。随后血栓素的产生率恢复到基线值。酵母聚糖激活血浆后，前列环素和乳酸脱氢酶的释放均未发生显著变化。在持续用10微摩尔丹曲林钠灌注的肝脏中，给予酵母聚糖激活血浆后血栓素产生也有类似变化。在酵母聚糖激活血浆输注期间，该组的灌注压力显著升高。这些结果证实了在离体兔肝模型中补体介导的血栓素产生，但未明确丹曲林敏感的细胞内钙释放在酵母聚糖激活血浆介导的血栓素产生机制中的作用。
