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尿苷和核苷酸对止血参数的影响。

Effects of uridine and nucleotides on hemostasis parameters.

作者信息

Arı Merve, Sağdilek Engin, Kılınç Evren, Cansev Mehmet, Özlük Kasım

机构信息

Vocational School of Health Services, KTO Karatay University, Konya, Turkey.

School of Medicine, Department of Biophysics, Bursa Uludağ University, Bursa, 16059, Turkey.

出版信息

J Thromb Thrombolysis. 2023 May;55(4):626-633. doi: 10.1007/s11239-023-02793-y. Epub 2023 Mar 24.

DOI:10.1007/s11239-023-02793-y
PMID:36961669
Abstract

Several purinergic receptors have been identified on platelets which are involved in hemostatic and thrombotic processes. The aim of the present study was to investigate the effects of uridine and its nucleotides on platelet aggregation and hemostasis in platelet-rich plasma (PRP) and whole blood. The effects of uridine, UMP, UDP, and UTP at different final concentrations (1 to 1000 µM) on platelet aggregation were studied using an aggregometer. In PRP samples, platelet aggregation was induced by ADP, collagen and epinephrine 3 min after addition of uridine, UMP, UDP, UTP and saline (as a control). All thromboelastogram experiments were performed at 1000 µM final concentrations of uridine and its nucleotides in whole blood. UDP and UTP were also tested in thromboelastogram with PRP. Our results showed that UDP, and especially UTP, inhibited ADP- and collagen-induced aggregation in a concentration-dependent manner. In whole blood thromboelastogram experiments, UDP stimulated clot formation while UTP suppressed clot formation. When thromboelastogram experiments were repeated with PRP, UTP's inhibitory effect on platelets was confirmed, while UDP's stimulated clot forming effect disappeared. Collectively, our data showed that UTP inhibited platelet aggregation in a concentration-dependent manner and suppressed clot formation. On the other hand, UDP exhibited distinct effects on whole blood or PRP in thromboelastogram. These data suggest that the difference on effects of UTP and UDP might have arisen from the different receptors that they stimulate and warrant further investigation with regard to their in vivo actions on platelet aggregation and hemostasis.

摘要

已在血小板上鉴定出几种嘌呤能受体,它们参与止血和血栓形成过程。本研究的目的是研究尿苷及其核苷酸对富血小板血浆(PRP)和全血中血小板聚集和止血的影响。使用血小板聚集仪研究了不同终浓度(1至1000 μM)的尿苷、UMP、UDP和UTP对血小板聚集的影响。在PRP样本中,在加入尿苷、UMP、UDP、UTP和生理盐水(作为对照)3分钟后,用ADP、胶原和肾上腺素诱导血小板聚集。所有血栓弹力图实验均在全血中尿苷及其核苷酸的终浓度为1000 μM的条件下进行。UDP和UTP也在PRP的血栓弹力图中进行了测试。我们的结果表明,UDP,尤其是UTP,以浓度依赖性方式抑制ADP和胶原诱导的聚集。在全血血栓弹力图实验中,UDP刺激凝块形成,而UTP抑制凝块形成。当用PRP重复血栓弹力图实验时,UTP对血小板的抑制作用得到证实,而UDP刺激凝块形成的作用消失。总体而言,我们的数据表明UTP以浓度依赖性方式抑制血小板聚集并抑制凝块形成。另一方面,UDP在血栓弹力图中对全血或PRP表现出不同的作用。这些数据表明,UTP和UDP作用的差异可能源于它们刺激的不同受体,有必要进一步研究它们对血小板聚集和止血的体内作用。

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1
Effects of uridine and nucleotides on hemostasis parameters.尿苷和核苷酸对止血参数的影响。
J Thromb Thrombolysis. 2023 May;55(4):626-633. doi: 10.1007/s11239-023-02793-y. Epub 2023 Mar 24.
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Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor.三种磷脂酶C激活型P2受体的尿苷核苷酸选择性:一种UDP选择性、一种UTP选择性以及一种ATP和UTP特异性受体的鉴定。
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本文引用的文献

1
Platelet Purinergic Receptors in Thrombosis and Inflammation.血小板嘌呤能受体在血栓形成和炎症中的作用。
Hamostaseologie. 2020 May;40(2):145-152. doi: 10.1055/a-1113-0711. Epub 2020 May 28.
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Accurate measurement of endogenous adenosine in human blood.准确测量人血液中的内源性腺苷。
PLoS One. 2018 Oct 25;13(10):e0205707. doi: 10.1371/journal.pone.0205707. eCollection 2018.
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Pharmacology of Adenosine Receptors: The State of the Art.腺苷受体药理学:最新进展。
Physiol Rev. 2018 Jul 1;98(3):1591-1625. doi: 10.1152/physrev.00049.2017.
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Purinergic Regulation of Neutrophil Function.嘌呤能调节中性粒细胞功能。
Front Immunol. 2018 Mar 1;9:399. doi: 10.3389/fimmu.2018.00399. eCollection 2018.
5
Biology of Platelet Purinergic Receptors and Implications for Platelet Heterogeneity.血小板嘌呤能受体的生物学特性及其对血小板异质性的影响
Front Pharmacol. 2018 Jan 30;9:37. doi: 10.3389/fphar.2018.00037. eCollection 2018.
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Platelets: an outlook from biology through evidence-based achievements in critical care.血小板:从生物学角度看重症监护领域基于证据的成就
Ann Transl Med. 2017 Nov;5(22):449. doi: 10.21037/atm.2017.11.04.
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Purinergic Signalling: Therapeutic Developments.嘌呤能信号传导:治疗进展
Front Pharmacol. 2017 Sep 25;8:661. doi: 10.3389/fphar.2017.00661. eCollection 2017.
8
Lipopolysaccharide (LPS) induced pulmonary neutrophil recruitment and platelet activation is mediated via the P2Y and P2Y receptors in mice.脂多糖(LPS)诱导的小鼠肺中性粒细胞募集和血小板活化是通过P2Y和P2Y受体介导的。
Pulm Pharmacol Ther. 2017 Aug;45:62-68. doi: 10.1016/j.pupt.2017.05.005. Epub 2017 May 6.
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Uridine Triphosphate Thio Analogues Inhibit Platelet P2Y Receptor and Aggregation.尿苷三磷酸硫代类似物抑制血小板P2Y受体和聚集。
Int J Mol Sci. 2017 Jan 29;18(2):269. doi: 10.3390/ijms18020269.
10
P2Y6 Receptor Antagonist MRS2578 Inhibits Neutrophil Activation and Aggregated Neutrophil Extracellular Trap Formation Induced by Gout-Associated Monosodium Urate Crystals.P2Y6受体拮抗剂MRS2578抑制痛风相关尿酸钠晶体诱导的中性粒细胞活化和聚集的中性粒细胞胞外陷阱形成。
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