白术内酯3抗血小板作用及其机制

目的：观察白术内酯3在体外对人血小板活化的影响，并探讨其可能的分子机制。方法通过体外血小板聚集实验，采用比浊法测定不同浓度白术内酯3对血栓烷类似物（U46619）诱发的人血小板聚集的影响；运用荧光素酶检测白术内酯3对血小板ATP分泌的影响；运用Western印迹法检测分子细胞外调节蛋白激酶（Erk1/2）、蛋白激酶B（Akt473）的磷酸化水平。结果白术内酯3可抑制U46619诱导下人血小板的体外聚集，其抑制效果具有浓度依赖性，各个浓度的实验组与DMSO对照组相比较，差异具有统计学意义（P＜0.01）；白术内酯3可抑制人血小板在U46619诱导下ATP的分泌且具有浓度依赖性，各个浓度的实验组与DMSO对照组相比较，差异具有统计学意义（P＜0.01）；经白术内酯3处理后人血小板活化信号通路中的Akt473、Erk1/2分子的磷酸化水平明显降低；与DMSO对照组相比，其差异具有统计学意义（P＜0.01）。结论白术内酯3对U46619诱导的人血小板聚集及分泌均能产生显著抑制作用，并影响其血小板活化过程中MAPK和PI3K-Akt信号通路。提示白术内酯3是一种有效的抗血小板化合物，有望成为新型抗血小板药物。

Inhibitory effects of atractylenolide 3 on platelet and its mechanism

Objective To study the effects of atractylenolide 3 on human platelet in vitro and explore the underlying mecha?nism. Methods The effects of atractylenolide 3 on human platelet aggregation induced by thrombus alkane analogues(U46619)was tested by turbidimetry in vitro. ATP secretion weas detected by luciferase detection,and the phosphorylation levels of Erk and Akt were detected by Western blotting. Results Atractylenolide 3 diminished U46619-induced human platelet aggregation in concentra?tion dependence. Compared with DMSO control group,the inhibitory rate were significant increased in each experiment group(P<0.01). Atractylenolide 3 inhibited adenosine triphosphate(ATP)secreted by human platclet in concentration dependence. Compared with the DMSO control group,the inhibitory rate were significant increased in each experiment group(P<0.01),and the levels of phospho-Akt(Ser473)and phospho-Erk1/2 were significant downregulated in the presence of atractylenolide 3 in each experiment group(P<0.01). Conclusion Atractylenolide 3 exhibits a concentration-dependent inhibitory effect on human platelet aggregation and secretion induced by U46619. Also,it regulated the MAPK and PI3K-Akt signaling pathways. These results show that atractyleno?lide 3 is an effective antiplatelet compound,may serve as new antithrombotic drugs.