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[三苯基氟化锡对兔血小板体外聚集、ATP分泌及丙二醛生成的影响]

[The effect of triphenyltin fluoride on aggregation, ATP secretion and malondialdehyde formation of rabbit platelets in vitro].

作者信息

Manabe S, Wada O, Matsui H, Ono T, Arakawa Y, Iwai H

出版信息

Sangyo Igaku. 1983 Jan;25(1):15-22. doi: 10.1539/joh1959.25.15.

Abstract

Recent studies have demonstrated that triphenyltin fluoride (TPTF), widely used as an agricultural chemical and a marine antifoulant, inhibits collagen-induced platelet aggregation and ATP secretion in rabbits ex vivo. The aim of the present investigation was to elucidate the mechanism of the inhibitory action of TPTF by investigating platelet malondialdehyde (MDA) formation, aggregation and ATP secretion following the stimulation by various stimuli of rabbit platelets treated in vitro with TPTF, other triphenyl metals and aspirin. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited dose-dependently both platelet aggregation and ATP secretion induced by collagen. The antiaggregating (IC50) concentration of TPTF was 6.0 X 10(-6) M against collagen. In addition, TPTF prevented the collagen-, and thrombin-induced formation of MDA, but had little inhibitory effect on the conversion of exogenous arachidonic acid to MDA in platelets. In contrast, aspirin (10(-3) M) inhibited platelet aggregation, ATP secretion and MDA formation induced by all the stimuli tested. Other triphenyl metals did not any inhibitory effect on collagen-, and sodium arachidonate-induced platelet aggregation and ATP secretion even at a final concentration at 10(-3) M. These results suggest that TPTF has a specific inhibitory effect on platelet aggregation and ATP secretion by acting at some step(s) of platelet membrane between the binding site of collagen and thrombin and the release of arachidonic acid.

摘要

最近的研究表明,广泛用作农业化学品和海洋防污剂的三苯基氟化锡(TPTF)在体外可抑制兔体内胶原蛋白诱导的血小板聚集和ATP分泌。本研究的目的是通过研究用TPTF、其他三苯基金属和阿司匹林体外处理的兔血小板在各种刺激下的血小板丙二醛(MDA)形成、聚集和ATP分泌,来阐明TPTF抑制作用的机制。虽然未发现TPTF对花生四烯酸钠诱导的血小板聚集和ATP分泌有抑制作用,但TPTF对胶原蛋白诱导的血小板聚集和ATP分泌均有剂量依赖性抑制作用。TPTF抗聚集(IC50)浓度对胶原蛋白为6.0×10(-6)M。此外,TPTF可抑制胶原蛋白和凝血酶诱导的MDA形成,但对血小板中外源性花生四烯酸转化为MDA的抑制作用很小。相比之下,阿司匹林(10(-3)M)抑制所有测试刺激诱导的血小板聚集、ATP分泌和MDA形成。其他三苯基金属即使在终浓度为10(-3)M时,对胶原蛋白和花生四烯酸钠诱导的血小板聚集和ATP分泌也没有任何抑制作用。这些结果表明,TPTF通过作用于血小板膜上胶原蛋白和凝血酶结合位点与花生四烯酸释放之间的某些步骤,对血小板聚集和ATP分泌具有特异性抑制作用。

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