川芎嗪通过抑制ERK5/P70S6K/Rac1信号通路发挥抗血小板活化及血栓形成作用  

Ligustrazine Inhibits Platelet Activation and Thrombus Formation Via ERK5/p70S6K/Rac1 Signaling

作　　者：张丽媛 陈璐[2] 李春晓 张璐莎 马璐璐 杨文杰 方乐玉 王倩怡 王虹 ZHANG Liyuan;CHEN Lu;LI Chunxiao;ZHANG Lusha;MA Lulu;YANG Wenjie;FANG Leyu;WANG Qianyi;WANG Hong(School of Integrative Medicine,Tianjin University of Traditional Chinese Medicine.Tianjin 301617,China;Tianjin University of Traditional Chinese Medicine,Institute of Chinese Medicine,Tianjin Key Laboratory of Modem Chinese Medicine,Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology,Tianjin 301617,China)

机构地区：[1]天津中医药大学中西医结合学院,天津301617 [2]方剂学教育部重点实验室,天津市中药药理学重点实验室,天津中医药大学中医药研究院,天津301617

出　　处：《中华中医药学刊》2021年第2期135-139,I0028,I0029,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家国际科技合作专项基金(2015DFA30430);国家自然科学基金青年科学基金(81603329)。

摘　　要：目的探讨川芎嗪抗血小板活化作用及其分子机制。方法运用缺氧诱导血小板损伤模型。采用比浊法检测血小板聚集,检测血小板在纤维蛋白原上的黏附,流式细胞术检测血小板CD62p的表达,CM-H2DCFDA染色检测血小板ROS的释放,Western blotting法检测ERK5、P70S6K、Rac1的磷酸化蛋白表达量,采用体内血栓形成试验检测川芎嗪对血栓的作用。结果川芎嗪可有效抑制血小板聚集,与模型组相比差异明显(P<0.01、P<0.001);与模型组比较,川芎嗪可显著抑制血小板在纤维蛋白原上的黏附,ROS的释放(P<0.05、P<0.001);同时川芎嗪能显著抑制血小板CD62p的表达,ERK5、P70S6K、Rac1的磷酸化,抑制血栓形成(P<0.05)。结论川芎嗪可通过ERK5/P70S6K/Rac1信号通路抑制血小板聚集、黏附、释放,从而抑制血栓形成。Objective To investigate the anti-platelet activation effect of ligustrazin and its molecular mechanism.Methods The hypoxia-induced platelet injury model was applied.Platelet aggregation was detected by turbidimetry.Platelet adhesion to fibrinogen was detected.Platelet CD62 p expression was detected by flow cytometry,and platelet ROS release was detected by CM-H2 DCFDA staining.The expressions of phosphorylated proteins of ERK5,P70 S6 K and Rac1 were detected by Western blotting,and the effect of ligustrazine on thrombus was detected by thrombosis test in vivo.Results Compared with the model group,ligustrazine could effectively inhibit platelet aggregation(P<0.01,P<0.001),and significantly inhibit platelet adhesion to fibrinogen and the release of ROS(P<0.05,P<0.001).Meanwhile,ligustrazine could significantly inhibit the expression of platelet CD62 p,phosphorylation of ERK5,P70 S6 K and Rac1,and thrombosis(P<0.05).Conclusion Ligustrazin can inhibit platelet aggregation,adhesion and release through ERK5/P70 S6 K/Rac1 signaling pathway,and thus inhibiting thrombosis.

关 键 词：川芎嗪 血小板 ERK5 颈总动脉血栓 

分 类 号：R285.5[医药卫生—中药学]