Antiplatelet Activity of Tetramethylpyrazine via Regulation of the P2Y12 Receptor Downstream Signaling Pathway.
Antiplatelet Activity of Tetramethylpyrazine via Regulation of the P2Y12 Receptor Downstream Signaling Pathway.
复制标题
四甲基吡嗪通过调节 P2Y12 受体下游信号通路的抗血小板活性
DOI：
10.1155/2022/7941039
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Shi D
中科院分区：
文献类型：
--
作者：
Guan B;Gao J;Tan Y;Ma X;Shi D
川芎嗪是一种具有抗血小板活性的中草药生物碱。TMP以多种方式抑制血小板活化。血小板5′二磷酸腺苷（ADP）P2 Y12受体在血小板功能、止血和血栓形成中起着重要作用。在这里，我们研究了TMP对P2 Y12受体相关的血小板功能的抑制作用。 使用激动剂诱导的血小板聚集、CD 62 p表达的流式细胞术分析、PAC-1活化和纤维蛋白凝块收缩来评估TMP的抑制潜力。在使用阻断剂抑制P2 Y12受体相关信号通路后，通过血小板聚集、CD 62 p表达和PAC-1活化来研究血小板活化。采用酶联免疫吸附试验（ELISA）检测环磷酸腺苷（cAMP）的分泌，采用蛋白质印迹法检测信号通路蛋白的表达、血管扩张剂刺激的磷蛋白的磷酸化和Akt的磷酸化。用ELISA法测定血小板炎症介质的释放。 TMP通过抑制ADP诱导的血小板聚集、P-选择素分泌、糖蛋白（GP）IIb/IIIa表达和减少动脉粥样硬化相关炎症介质（sCD 40 L和IL-1β）的释放而具有抗血小板作用。TMP减少了凝块收缩的面积，反映了GPIIb/IIIa活化的抑制。TMP通过增加cAMP生成、VASPser 157磷酸化和Akt去磷酸化抑制腺苷二磷酸诱导的血小板活化。 TMP通过P2 Y12受体相关信号通路选择性抑制ADP诱导的血小板活化。
Tetramethylpyrazine (TMP) is an alkaloid in Chinese herbal medicine, which possesses antiplatelet activity. TMP inhibits platelet activation in many ways. The platelet P2Y12 receptor for adenosine 5′ diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Here, we investigated the inhibitory effect of TMP on P2Y12 receptor-related platelet function. The inhibitory potential of TMP was assessed using agonist-induced platelet aggregation, flow cytometric analysis of CD62p expression, PAC-1 activation, and fibrin clot retraction. After the P2Y12 receptor-related signaling pathway was inhibited using the blocker, platelet activation was studied by platelet aggregation, CD62p expression, and PAC-1 activation. The secretion of cyclic adenosine monophosphate (cAMP) was measured using enzyme-linked immunosorbent assay (ELISA), and the expression of signaling pathway protein, phosphorylation of vasodilator-stimulated phosphoprotein, and phosphorylation of Akt were investigated using western blotting. The release of platelet inflammatory mediators was measured using ELISA. TMP had an antiplatelet effect by inhibiting ADP-induced aggregation, P-selectin secretion, and glycoprotein (GP) IIb/IIIa expression and reducing the release of atherosclerotic-related inflammatory mediators (sCD40L and IL-1β). TMP decreased the area of clot retraction, reflecting inhibition of GPIIb/IIIa activation. TMP inhibited adenosine diphosphate-induced platelet activation via increased cAMP production, VASPser157 phosphorylation, and Akt dephosphorylation. TMP selectively inhibits ADP-induced platelet activation via P2Y12 receptor-related signaling pathways.