Inhibition of platelet aggregation by putrescine, spermidine, and spermine in hypercholesterolemic rabbits
Inhibition of platelet aggregation by putrescine, spermidine, and spermine in hypercholesterolemic rabbits
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DOI：
10.1016/s0188-4409(00)00238-1
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发表时间：
2000-11-01
影响因子：
7.7
通讯作者：
Méndez, JD
中科院分区：
文献类型：
--
作者：
de la Peña, HC;Sosa-Melgarejo, JA;Méndez, JD
背景资料。高胆固醇血症会引起血小板功能的改变。血小板过度聚集被认为是动脉粥样硬化的易感因素。本文研究了多胺类化合物腐胺、亚精胺和精胺对正常和高胆固醇血症兔血小板的抗聚集作用。新西兰兔被喂以高胆固醇饮食10周。测定血清中血脂和血糖。用来自对照组和胆固醇喂养的兔的富含血小板血浆(PRP)进行了血小板聚集的测定。用2.5mU/mLADP和2mUg/mL胶原作为血小板聚集诱导剂。结果饲喂胆固醇后，血清总胆固醇和低密度脂蛋白浓度分别从2 6.3+/-8.1 mg/dL和15.9+/-5.9 mg/dL增加到1,383.8+/-5 8.9 mg/dL，甘油三酯浓度从88.3+/-35.6 mg/dL增加到411.0+/-151.5 mg/dL。10 mU的多胺对正常兔的PRP有75%的血小板聚集抑制作用。以ADP为激动剂时，精胺对高胆固醇血症兔PRP的血小板聚集抑制作用达54%。多胺的作用顺序为精胺、亚精胺、腐胺。此外，我们还发现，高胆固醇血症患者的血小板精氨酸酶活性和L-精氨酸含量无明显变化。这些结果表明，多胺类化合物腐胺、亚精胺和精胺对血小板聚集有拮抗作用，提示在正常和高胆固醇血症条件下，多胺类物质在血小板聚集中起着关键作用。(C)2001年国际管理和社会保障制度。爱思唯尔科学公司出版。
Background. Hypercholesterolemia causes alterations in platelet function. Platelet hyper-aggregation is considered a predisposing factor for atherosclerosis. In this paper, the anti-aggregating effect of the polyamines putrescine, spermidine, and spermine was studied on platelets of normal and hypercholesterolemic rabbits.Methods. New Zealand rabbits were fed with a cholesterol-enriched diet for 10 weeks. Lipids and glucose were determined in serum. The assays of platelet aggregation were carried out using platelet-rich plasma (PRP) obtained from both control and cholesterol-fed rabbits. We used 2.5 mu mol/mL ADP and 2 mug/mL collagen as inductors of platelet aggregation. In addition, arginase activity and L-arginine content were determined in PRP.Results, Serum total cholesterol and LDL-cholesterol concentrations were increased from 26.3 +/- 8.1 to 1.485.0 +/- 26.8 mg/dL and from 15.9 +/- 5.9 to 1,383.8 +/- 58.9 mg/dL, respectively, whereas triglyceride concentration increased from 88.3 +/- 35.6 to 411.0 +/- 151.5 mg/dL upon cholesterol feeding. Seventy-five percent of platelet aggregation inhibition was observed with 10 muM of polyamines in PRP of normal rabbits. Spermine inhibited platelet aggregation by 54% in PRP of hypercholesterolemic rabbits when ADP was used as agonist. The order of polyamine action was spermine > spermidine > putrescine. In addition, we found that platelet arginase activity and L-arginine content were unaltered upon hypercholesterolemia.Conclusions. These results show that the polyamines putrescine, spermidine, and spermine have antagonist action in platelet aggregation and suggest a key role of polyamines in platelet aggregation under normal and hypercholesterolemic conditions. (C)2001 IMSS. Published by Elsevier Science Inc.