Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan.
Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate 028-3695, Japan.
J Stroke Cerebrovasc Dis. 2021 Mar;30(3):105547. doi: 10.1016/j.jstrokecerebrovasdis.2020.105547. Epub 2020 Dec 22.
The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA).
PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants.
In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited.
We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.
尚未完全阐明 P2Y12 受体拮抗剂对 PAR1 和 PAR4 激活肽（AP）诱导的血小板聚集的抑制作用。本研究旨在使用包括中风或短暂性脑缺血发作（TIA）患者在内的个体的富含血小板的血浆（PRP），研究 P2Y12 受体拮抗剂对 PAR1 和 PAR4-AP 诱导的血小板聚集的抑制作用。
在体外用坎格雷洛预处理的 10 名健康个体的 PRP 中加入二磷酸腺苷（ADP）、PAR4-AP 或 PAR1-AP 进行刺激。此外，从 2017 年 12 月至 2019 年 4 月我院收治的 148 例急性缺血性中风或 TIA 连续患者中招募了 20 例患者。同样用这些激动剂刺激每位患者开始使用氯吡格雷前和>7 天后获得的 PRP。所有参与者的血小板聚集均使用自动凝血分析仪进行测量。
在健康个体中，ADP 和 PAR4-AP 诱导的血小板聚集在体外依赖坎格雷洛浓度显著抑制，而 PAR1-AP 诱导的血小板聚集被轻微抑制。在中风或 TIA 患者中，氯吡格雷在所有浓度下均抑制 ADP 诱导的血小板聚集，并且在 50µmol/L 的 PAR4-AP 时显著抑制 PAR4-AP 诱导的血小板聚集（p<0.05），特别是在对 PAR4-AP 反应性高的 5 名患者中。PAR1-AP 诱导的血小板聚集也被轻微抑制。
我们在对 PAR4-AP 反应性高的中风或 TIA 患者中，显示氯吡格雷对 PAR4-AP 诱导的血小板聚集具有显著的抑制作用。
