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大鼠血小板的聚集与抑制以及内过氧化物代谢产物的形成。

Aggregation and inhibition of rat platelets, and the formation of endoperoxide metabolites.

作者信息

Hwang D H

出版信息

Prostaglandins Med. 1980 Sep;5(3):163-73.

PMID:7413850
Abstract

In citrated rat platelets, arachidonic acid (AA) at 1 mM could not induce aggregation unlike human or rabbit platelets. However, preincubation of platelet rich plasma (PRP) prepared in sodium citrate with AA (1 mM) enhanced the aggregation induced by collagen suspension or adenosine diphosphate (ADP), and this enhancement was abolished by the preincubation of PRP with indomethacin. Arachidonic acid at a higher concentration (6 mM) induced aggregation; but it was not attenuated by preincubation of indomethacin indicating that this aggregation may not be augmented by prostaglandins (PGs) or their intermediates. The major product of endoperoxide metabolites formed during collagen-induced aggregation was thromboxane A2 (TXA2) as measured in terms of TXB2, the stable metabolite. Preincubation of citrated PRP with imidazole neither abolished the enhancement of ADP-induced or collagen-induced aggregation by AA (1mM), nor attenuated the aggregation induced by ADP or collagen alone; but imidazole inhibited the synthesis of TXB2 by more than 90%. In heparinized platelets, arachidonic acid at 0.25 mM induced the aggregation, and this was inhibited by preincubation of the PRP with indomethacin. Heparinized PRP was much more sensitive to aggregating agents than citrated PRP. This implied that aggregation of rat platelets is more dependent on calcium than human o rabbit platelets. Preincubation of heparinized PRP with imidazole inhibited AA-induced aggregation, and the inhibition was abolished by the preincubation of vitamin E. This result implied that inhibition of AA-induced aggregation by imidazole is due to products of platelet lipoxygenase rather than due to the inhibition of TXA2 synthesis.

摘要

在枸橼酸化的大鼠血小板中,与人类或兔血小板不同,1 mM的花生四烯酸(AA)不能诱导聚集。然而,用AA(1 mM)对在枸橼酸钠中制备的富血小板血浆(PRP)进行预孵育,可增强胶原悬液或二磷酸腺苷(ADP)诱导的聚集,且吲哚美辛对PRP的预孵育可消除这种增强作用。较高浓度(6 mM)的花生四烯酸可诱导聚集;但吲哚美辛预孵育不能使其减弱,这表明这种聚集可能不会被前列腺素(PGs)或其中间体增强。以稳定代谢产物TXB2衡量,胶原诱导聚集过程中形成的内过氧化物代谢产物的主要产物是血栓素A2(TXA2)。用咪唑对枸橼酸化PRP进行预孵育,既不能消除AA(1 mM)对ADP诱导或胶原诱导聚集的增强作用,也不能减弱单独由ADP或胶原诱导的聚集;但咪唑可抑制TXB2的合成达90%以上。在肝素化血小板中,0.25 mM的花生四烯酸可诱导聚集,且PRP用吲哚美辛预孵育可抑制这种聚集。肝素化PRP比枸橼酸化PRP对聚集剂更敏感。这意味着大鼠血小板的聚集比人类或兔血小板更依赖于钙。用咪唑对肝素化PRP进行预孵育可抑制AA诱导的聚集,且维生素E的预孵育可消除这种抑制作用。这一结果表明,咪唑对AA诱导聚集的抑制作用是由于血小板脂氧合酶的产物,而非由于对TXA2合成的抑制。

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引用本文的文献

1
Characteristics of the formation of the platelet lipoxygenase product from endogenous arachidonic acid.
Lipids. 1982 Dec;17(12):845-7. doi: 10.1007/BF02534576.
2
Effects of dietary 9-trans, 12-trans linoleate on arachidonic acid metabolism in rat platelets.膳食9-反式、12-反式亚油酸对大鼠血小板中花生四烯酸代谢的影响。
Lipids. 1982 Apr;17(4):307-13. doi: 10.1007/BF02534946.
3
In vitro and in vivo effects of ethanol on the formation of endoperoxide metabolites in rat platelets.乙醇对大鼠血小板中内过氧化物代谢产物形成的体外和体内效应。
Lipids. 1981 Aug;16(8):583-8. doi: 10.1007/BF02534903.