Hernandez M R, Tonda R, Pino M, Serradell M, Arderiu G, Escolar G
Hospital Clínic i Provincial, Barcelona, Spain.
Eur J Clin Invest. 2004 Apr;34(4):297-302. doi: 10.1111/j.1365-2362.2004.01334.x.
Cyclooxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs have been used for anti-inflammatory therapy. However, it has also been described that they may increase risk of cardiovascular events.
To study the effects of COX2 inhibitor rofecoxib on platelet function using in vitro tests. Results were compared with those obtained in a parallel experiment with acetyl salicylic acid (ASA).
Studies of platelet aggregation, using different agonists, were performed by a turbidimetric method. Adhesive and cohesive function of platelets were analyzed by perfusion techniques, treated blood was exposed to thrombogenic surfaces and platelet interaction was morphometrically evaluated.
Twenty-five micro M of rofecoxib induced a prolonged lag time and a reduction in the percentage of aggregation when arachidonic acid, ADP or collagen were used as agonists. In perfusion studies with parallel chamber rofecoxib 50 microM and ASA 500 microM reduced overall platelet interaction with the collagen surface (17.4 +/- 3.7, P < 0.05; vs. 32.1 +/- 2.6%P < 0.05 and 17.9 +/- 2.4, vs. 31.9 +/- 3.24, P < 0.05, respectively). In studies performed on annular chambers, 25 micro M of rofecoxib reduced platelet interaction; values of the thrombus and covered surface were 17.4 +/- 4.5%; P < 0.05 and 21.1 +/- 4.1%; P < 0.05, respectively, vs. 30.4 +/- 7.5% and 33.5 +/- 6.5 in the control. ASA did also impair thrombus formation but differences did not reach the levels of statistical significance. Moreover, rofecoxib but not ASA reduced significantly thrombus height and thrombus area (7.4 +/- 0.5 microM; P < 0.005 and 96.0 +/- 21.2 microM(2); P < 0.05 vs. control 11.2 +/- 0.9 microM and 220.0 +/- 47.7 microM(2), respectively).
We conclude that under our experimental conditions, rofecoxib diminished platelet aggregation induced by different agonists and inhibited platelet-mediated thrombogenesis in an in vitro model of thrombosis.
环氧化酶（COX）-2选择性非甾体抗炎药已用于抗炎治疗。然而，也有描述称它们可能会增加心血管事件的风险。
使用体外试验研究COX2抑制剂罗非昔布对血小板功能的影响。将结果与在乙酰水杨酸（ASA）平行实验中获得的结果进行比较。
采用比浊法，使用不同激动剂进行血小板聚集研究。通过灌注技术分析血小板的黏附与凝聚功能，将处理过的血液暴露于致血栓表面，并对血小板相互作用进行形态学评估。
当使用花生四烯酸、ADP或胶原作为激动剂时，25微摩尔的罗非昔布可诱导较长的延迟时间并降低聚集百分比。在平行腔室的灌注研究中，50微摩尔的罗非昔布和500微摩尔的ASA均降低了血小板与胶原表面的总体相互作用（分别为17.4±3.7，P<0.05；与32.1±2.6%，P<0.05以及17.9±2.4，与31.9±3.24，P<0.05）。在环形腔室进行的研究中，25微摩尔的罗非昔布减少了血小板相互作用；血栓和覆盖表面的值分别为17.4±4.5%；P<0.05和21.1±4.1%；P<0.05，而对照组分别为30.4±7.5%和33.5±6.5%。ASA也损害了血栓形成，但差异未达到统计学显著水平。此外，罗非昔布而非ASA显著降低了血栓高度和血栓面积（分别为7.4±0.5微摩尔；P<0.005和96.0±21.2平方微米；P<0.05，而对照组分别为11.2±0.9微摩尔和220.0±47.7平方微米）。
我们得出结论，在我们的实验条件下，罗非昔布减少了不同激动剂诱导的血小板聚集，并在体外血栓形成模型中抑制了血小板介导的血栓形成。
