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从赤子爱胜蚓体腔液中提取的多糖-蛋白复合物具有多途径抗血小板作用,且无凝血障碍和细胞毒性。

Polysaccharide-protein complex from coelomic fluid of Dendrobaena veneta earthworm exerts a multi-pathway antiplatelet effect without coagulopathy and cytotoxicity.

机构信息

Department of Environmental Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland.

Department of Environmental Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland.

出版信息

Biomed Pharmacother. 2022 Jul;151:113205. doi: 10.1016/j.biopha.2022.113205. Epub 2022 May 26.

Abstract

There is a pressing need to identify novel antiplatelet agents, an alternative to acetylsalicylic acid and thienopyridines, to broaden the prevention of cardiovascular events, the leading cause of global morbidity and mortality. Invertebrate coelomocytes structurally and functionally resemble the thrombocyte-like cells of vertebrates; therefore, the coelomic fluid in which they are suspended may contain agents controlling their clumping abilities. However, whether coelomocytes-free coelomic fluid may also affect human platelet activities was not a subject of any study. This study aimed to screen the in vitro antiplatelet and anticoagulant activities of the polysaccharide-protein complex from Dendrobaena veneta coelomic fluid (25-100 µg/mL) (PPC-DV). All tested fluid concentrations induced significant (42.4-52.5%) inhibition of adenosine-5'-diphosphate (ADP)-induced aggregation of human platelets at a level comparable to that of 140 µmol/L acetylsalicylic acid. Its relevant antiplatelet effect (27.2-45.9%) was also evidenced in the thrombin receptor-activating peptide-6 (TRAP-6) assay. Moreover, 50 and 100 µg/mL of PPC-DV inhibited arachidonic acid-inducible aggregation. No coagulopathic or cytotoxic effects of PPC-DV were observed. The study indicates that PPC-DV, at a concentration of at least 50 µg/mL, exerts a favorable antiplatelet effect by targeting at least three pathways (P2Y receptor, cyclooxygenase-1, and protease-activated receptor-1), justifying further experimental and clinical investigations on its use in cardiovascular disease prevention.

摘要

迫切需要确定新型抗血小板药物,以替代乙酰水杨酸和噻吩吡啶,从而扩大预防心血管事件的范围,心血管事件是全球发病率和死亡率的主要原因。无脊椎动物体腔细胞在结构和功能上与脊椎动物的血小板样细胞相似;因此,它们悬浮其中的体腔液中可能含有控制其聚集能力的物质。然而,体腔液中不含体腔细胞是否也会影响人类血小板的活性,这并不是任何研究的主题。本研究旨在筛选来自光壳参属涡虫体腔液(25-100μg/ml)的多糖-蛋白复合物(25-100μg/ml)(PPC-DV)的体外抗血小板和抗凝活性。所有测试的液体浓度均能显著抑制(42.4-52.5%)人血小板对二磷酸腺苷(ADP)诱导的聚集,其抑制水平与 140μmol/L 乙酰水杨酸相当。在凝血酶受体激活肽-6(TRAP-6)检测中也证实了其相关的抗血小板作用(27.2-45.9%)。此外,50 和 100μg/ml 的 PPC-DV 抑制花生四烯酸诱导的聚集。PPC-DV 未观察到凝血异常或细胞毒性作用。该研究表明,PPC-DV 在至少 50μg/ml 的浓度下,通过至少三种途径(P2Y 受体、环氧化酶-1 和蛋白酶激活受体-1)发挥有利的抗血小板作用,这证明了进一步在心血管疾病预防中使用 PPC-DV 的实验和临床研究是合理的。

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