FGF-21对大鼠血小板聚集和活化的抑制作用

临床上大部分抗血小板药物存在继发性出血等副作用,亟需寻找一种安全有效的抗血小板药物。二磷酸腺苷(ADP)和花生四烯酸(AA)是介导血小板聚集的主要物质,文章探讨成纤维细胞生长因子-21(FGF-21)是否抑制ADP或AA诱导大鼠血小板聚集和活化。将大鼠分为正常对照组、正常鼠血小板活化组、阿司匹林干预后血小板活化组、FGF-21高、中、低剂量干预后血小板活化组。给药干预后提取各组血小板,分别用ADP或AA处理,观察处理后血小板聚集情况以及P选择素和血栓素(TXB2)表达水平。与正常对照组相比,正常鼠血小板经ADP或AA处理活化后,血小板聚集率显著升高,血浆中P选择素和TXB2含量明显上升;与正常鼠血小板经ADP或AA处理活化后相比,经阿司匹林和FGF-21干预后分别经ADP或AA处理活化后的血小板聚集率显著下降,血浆中P选择素和TXB2含量显著下降;FGF-21干预组经ADP或AA活化后,血小板聚集率、P选择素和TXB2含量下降水平呈明显剂量依赖性。目前国内外尚未发现FGF-21对血小板聚集与活化作用的相关报道,研究首次证明FGF-21具有抑制ADP和AA诱导血小板聚集和活化作用及明显的抗血凝作用,填补FGF-21在抗血凝研究领域空白,为开发安全有效的抗血凝药物提供理论依据。

Inhibitory effect of FGF-21 on platelet aggregation and activation in rats

At present, many anti-platelet drugs have side effects such as secondary bleeding, so it is urgent to find a safe and effective anti-platelet drug. Adenosine diphosphate(ADP) and arachidonic acid(AA) are two major pathways mediating platelet aggregation. This study aimed to investigate whether fibroblast growth factor-21(FGF-21) inhibited ADP or AA-induced platelet aggregation and activation in rats. The rats were divided into the normal control group, the normal platelet activation group, the platelet activation group after aspirin preventive intervention, and the platelet activation group after preventive intervention by high, medium and low doses FGF-21. After intervention, platelets in each group were extracted and treated with ADP or AA, respectively. Platelet aggregation, as well as the expression levels of P-selectin and thrombin(TXB2) after ADP or AA treatment. Compared with the normal control group, the platelet aggregation rate of normal rats was significantly increased after activated by ADP or AA treatment, and the content of P-selectin and TXB2 in plasma was also significantly increased. Compared with the normal platelets activated by ADP or AA treatment, the aggregation rate of platelets and the content of P-selectin and TXB2 in plasma activated by ADP or AA treatment were significantly reduced after aspirin or FGF-21 preventive intervention. In addition, the platelet aggregation rate, P-selectin and TXB2 content were reduced in a dose-dependent manner after preventive intervention by high, medium and low doses FGF-21 followed by the activation with ADP and AA. So far, there is no report about effect of FGF-21 on platelet aggregation and activation. The study was the first time to find that FGF-21 had the effect of inhibiting platelet aggregation and activation induced by ADP and AA, it had obvious anticoagulant effect. The study opens a new research direction for FGF-21 and provides a theoretical basis for the development of safe and effective anticoagulant drugs.