Quinn Martin J, Bhatt Deepak L, Zidar Frank, Vivekananthan Deepak, Chew Derek P, Ellis Stephen G, Plow Edward, Topol Eric J
St. Vincents University Hospital, Dublin, Ireland.
Am J Cardiol. 2004 Mar 15;93(6):679-84. doi: 10.1016/j.amjcard.2003.11.048.
Platelets play an important role in the inflammatory response. In a nonrandomized comparison, we examined the effect of clopidogrel pretreatment on platelet inflammatory marker expression in patients undergoing percutaneous coronary intervention (PCI). Platelet expression of the inflammatory markers CD40 ligand (L) and CD62 P-selectin (P) and serum levels of interleukin-6 and CD40L were compared in patients pretreated (>24 hours before PCI) or not pretreated with clopidogrel. Blood samples were obtained before and after the procedure, and from 18 to 24 hours later. Marker expression in resting and adenosine diphosphate (ADP) (50 micromol/L) and thrombin receptor activating peptide (TRAP) (10 micromol/L) activated samples was quantified by flow cytometry. Serum CD40L and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Seventy-nine patients were recruited into the study. Forty-two percent were pretreated with clopidogrel for a median of 5 days (range 1 to 1,325). Clopidogrel pretreatment was associated with lower ADP-activated platelet CD40L expression in baseline and postprocedural samples. Similarly, platelet CD62P expression at all time points in ADP-activated and in baseline and postprocedural TRAP-activated samples was lower in patients pretreated with clopidogrel. These differences remained after multivariate adjustment between the groups. Serum CD40L levels increased from 2.13 +/- 2.37 ng/ml at baseline to 4.77 +/- 3.86 ng/ml at 18 to 24 hours after the procedure (p <0.0001). Similarly, serum IL-6 levels increased at 18 to 24 hours after the procedure (14.8 +/- 42.0 pg/ml before vs 25.5 +/- 36.0 pg/ml at 18 to 24 hours after the procedure, p <0.0001). Clopidogrel pretreatment did not affect serum IL-6 or CD40L levels. Thus, clopidogrel pretreatment reduces platelet inflammatory marker expression in patients undergoing PCI.
血小板在炎症反应中起重要作用。在一项非随机对照研究中,我们检测了氯吡格雷预处理对接受经皮冠状动脉介入治疗(PCI)患者血小板炎症标志物表达的影响。比较了氯吡格雷预处理(PCI前>24小时)或未预处理患者的炎症标志物CD40配体(L)和CD62 P-选择素(P)的血小板表达以及白细胞介素-6和CD40L的血清水平。在手术前后以及术后18至24小时采集血样。通过流式细胞术对静息和二磷酸腺苷(ADP)(50 μmol/L)及凝血酶受体激活肽(TRAP)(10 μmol/L)激活样本中的标志物表达进行定量。血清CD40L和白细胞介素(IL)-6水平通过酶联免疫吸附测定法测定。79名患者纳入本研究。42%的患者接受氯吡格雷预处理,中位时间为5天(范围1至1325天)。氯吡格雷预处理与基线和术后样本中ADP激活的血小板CD40L表达降低有关。同样,在ADP激活以及基线和术后TRAP激活样本的所有时间点,氯吡格雷预处理患者的血小板CD62P表达均较低。两组间多因素调整后这些差异依然存在。血清CD40L水平从基线时的2.13±2.37 ng/ml增加至术后18至24小时的4.77±3.86 ng/ml(p<0.0001)。同样,术后18至24小时血清IL-6水平升高(术前14.8±42.0 pg/ml,术后18至24小时为25.5±36.0 pg/ml,p<0.0001)。氯吡格雷预处理不影响血清IL-6或CD40L水平。因此,氯吡格雷预处理可降低接受PCI患者的血小板炎症标志物表达。