辛伐他汀通过过氧化物酶体增殖物激活受体激活抑制胶原诱导的血小板活化

EFFECTS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN SIMVASTATIN INHIBITION ON COLLAGEN-INDUCED PLATELET ACTIVATION

目的探讨辛伐他汀体外恒温孵育对胶原诱导的血小板活化的影响及相关机制。方法采集河北医科大学第二医院门诊健康成人志愿者外周静脉血,并制备血小板悬液,应用全血阻抗法、流式细胞术、酶联免疫吸附测定及荧光分光光度法测定不同浓度辛伐他汀体外孵育对胶原诱导的血小板聚集及活化的影响,检测辛伐他汀体外孵育对血小板胞浆过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPARs)活化的影响,以及PPARs活化后对血小板功能的作用。结果辛伐他汀体外孵育可活化PPARs(P<0.05),并可通过活化PPARγ进而抑制胶原诱导的血小板聚集、活化标志物表达以及胞浆钙离子浓度升高。结论辛伐他汀可通过PPARγ激活抑制胶原诱导的血小板活化。

Objective To examine the mechanisms by which the peroxisome proliferator-activated receptors （PPARs ）-mediated pathways contribute to the antiplatelet activity of simvastatin.Methods Blood samples were donated from healthy volunteers in order to prepare human platelet suspensions.The effects of simvastatin on collagen-induced platelet activation and the activity of PPARs were measured by impedance aggregometry,flow cytometric analysis, enzyme-linked immunosorbent assay,and spectrofluorimetry.Results Simvastatin induced PPARα and PPARγ activation in a dose-dependent manner in platelet suspensions （P 〈 0.05）. Additionally,simvastatin inhibited collagen-induced platelet aggregation,expression of CD62 and PAC-1,and Ca2＋ mobilization.These effects of simvastatin on platelet responses were strongly reduced by adding selective PPARγ antagonist （P 〈0.05）,but not PPARα antagonist.Conclusion Simvastin inhibition of platelet activation induced by collagen is mediated by PPARγ-dependent processes.