Hsiao G, Yen M H, Lee Y M, Sheu Joen-Rong
Graduate Institute of Medical Sciences, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan.
Br J Haematol. 2002 Jun;117(3):699-704. doi: 10.1046/j.1365-2141.2002.03492.x.
Platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. PMC (2, 2, 5, 7, 8-pentamethyl-6-hydroxychromane; 20 microg/g, i.v.) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules. When fluorescein sodium was given at 10 microg/kg, PMC (20 microg/g) delayed occlusion time by about 1.7-fold. Furthermore, aspirin (250 microg/g) also showed similar activity in delaying the occlusion time. On a molar basis, PMC was about 14-fold more potent than aspirin at delaying the occlusion time. PMC was also effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 5 and 10 microg/g. In addition, intravenous injection of PMC (5 microg/g) significantly prolonged bleeding time by about 1.6-fold compared with normal saline in severed mesenteric arteries of rats. Continuous infusion of PMC (1 microg/g/min) significantly increased the bleeding time by about 1.6-fold and the bleeding time was also significantly prolonged for up to 90 min after cessation of PMC infusion. These results suggest that PMC has an effective antiplatelet effect in vivo and may be a potential therapeutic agent for arterial thrombosis, but must be assessed further for toxicity.
在用荧光素钠进行静脉预处理的小鼠中，通过用滤光照射肠系膜小静脉诱导血小板血栓形成。PMC（2,2,5,7,8 - 五甲基 - 6 - 羟基色满；20微克/克，静脉注射）显著延长了肠系膜小静脉中诱导血小板栓形成的潜伏期。当以10微克/千克给予荧光素钠时，PMC（20微克/克）使闭塞时间延迟约1.7倍。此外，阿司匹林（250微克/克）在延迟闭塞时间方面也表现出类似的活性。以摩尔为基础，在延迟闭塞时间方面，PMC的效力约为阿司匹林的14倍。当以5和10微克/克的剂量静脉给药时，PMC在降低小鼠ADP诱导的急性肺血栓栓塞死亡率方面也有效。此外，与大鼠切断的肠系膜动脉中的生理盐水相比，静脉注射PMC（5微克/克）使出血时间显著延长约1.6倍。持续输注PMC（1微克/克/分钟）使出血时间显著增加约1.6倍，并且在停止PMC输注后长达90分钟出血时间也显著延长。这些结果表明，PMC在体内具有有效的抗血小板作用，可能是动脉血栓形成的潜在治疗剂，但必须进一步评估其毒性。
