Evaluation of inhibitory effects of anti-platelet agents on platelet aggregation -Usefulness of P-selectin as a marker of platelet activation-

抗血小板药物对血小板聚集的抑制效果评价 -P-选择素作为血小板活化标志物的用途-

• 批准号: 13672395
• 负责人: YAMADA Katsushi
• 金额: $ 2.24万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672395/
• 关键词: anti-platelet agent; platelet aggregation; aspirin; atolvastatin; platelet-rich plasma aggregation; whole blood aggregation; coronary artery bypass grafting; P-selectin; 冠動脈バイパス術; sP-セレクチン; トロンボキサンB2; PATI値; 全血血小板凝集; 光透過法; ADP

Firstly, we evaluated anti-platelet aggregatory effects of aspirin, cilostazol and ramatroban on platelet-rich plasma (PRP) and whole blood. We obtained results that these drugs suppressed PRP aggregation and release reaction of soluble P-selectin (sP-selectin), transforming growth factor (TGF-β1) and thromboxane (TX) B2 in response to ADP, collagen and arachidonic acid. The inhibitory effects of these drugs were dependent on the agonists. In addition, these drugs suppressed whole blood aggregation in response to ADP. Secondary, we estimated the usefulness of the combination of aspirin with atolvastatin (combined therapy group) on human platelet aggregation in patients receiving CABG. We obtained results as follows ; 1)the levels of total cholesterol in combined therapy group on POD-14 significantly decreased when compared with those in aspirin alone (monotherapy) group, 2)inflammatory markers in combined therapy group on POD-3 and -7 were significantly lower than those in monotherapy group, 3)circulating levels of the molecules in combined therapy group on POD-14 were significantly lower than those in monotherapy group, 4)On POD-14, PRP aggregation and the release of the molecules in response to ADP in combined therapy were significantly suppressed when compared with those in momotherapy. These results suggest that sP-selectin is a useful marker in detecting platelet activation, and atolvastatin may suppress the activation of platelet and combined therapy of aspirin and atolvastatin may be useful for the patients with angina pectoris complicated hypercholesterolemia.

首先，我们评估了阿司匹林、西洛他唑和雷马曲班对富血小板血浆（PRP）和全血的抗血小板聚集作用。我们得到的结果是，这些药物抑制了 PRP 聚集以及可溶性 P-选择素（sP-选择素）、转化生长因子（TGF-β1）和血栓素（TX）B2 响应 ADP、胶原蛋白和花生四烯酸的释放反应。这些药物的抑制作用取决于激动剂。此外，这些药物还抑制 ADP 引起的全血聚集。其次，我们评估了阿司匹林与阿托伐他汀联合用药（联合治疗组）对接受 CABG 的患者血小板聚集的有效性。我们得到的结果如下； 1）联合治疗组POD-14总胆固醇水平较单用阿司匹林（单一治疗）组显着降低，2）联合治疗组POD-3和-7炎症标志物显着低于单药治疗组，3）联合治疗组POD-14循环分子水平显着低于单药治疗组，4）POD-14、PRP 与 MOMO 疗法相比，联合疗法中 ADP 响应的分子聚集和释放被显着抑制。这些结果表明sP-选择素是检测血小板活化的有用标志物，阿托伐他汀可能抑制血小板的活化，阿司匹林和阿托伐他汀联合治疗可能对心绞痛并发高胆固醇血症患者有用。