丹酚酸A抑制血小板及中性粒细胞活化作用  

Salvianolic acid A inhibits platelet and neutrophil activation

作　　者：杨文杰 王洪颖 马璐璐 方乐玉 李春晓 张璐莎 张丽媛 王倩怡 孙伟 冷雨泽 薛岳进 李梦瑶 陈璐[3] 王虹 YANG Wen-jie;WANG Hong-ying;MA Lu-lu;FANG Le-yu;LI Chun-xiao;ZHANG Lu-sha;ZHANG Li-yuan;WANG Qian-yi;SUN Wei;LENG Yu-ze;XUE Yue-jin;LI Meng-yao;CHEN Lu;WANG Hong(School of Integrative Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Rehabilitation Center of Joint Logistics Support Force of Chinese People's Liberation Army,Tianjin 300141,China;State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,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]中国人民解放军联勤保障部队天津康复疗养中心,天津300141 [3]天津中医药大学组分中药国家重点实验室,天津301617

出　　处：《中国药理学通报》2022年第5期740-748,共9页Chinese Pharmacological Bulletin

基　　金：国家国际科技合作专项(No 2015DFA30430);国家自然科学基金青年项目(No 81603329)。

摘　　要：目的探究丹酚酸A(Salvianolic acid A,SAA)对心肌梗死(myocardial infarction,MI)小鼠心脏的血小板募集、活化及中性粒细胞的影响。方法将C57BL/6小鼠随机分为:假手术组、MI模型组、SAA(5、10 mg·kg^(-1))组、替罗非班(tirofiban,0.87 mg·kg^(-1))组,尾静脉注射给药3 d。超声心动、HE染色检测小鼠心功能及梗死面积;采用IHC、FCS、ELISA、Western blot等方法探讨了SAA抑制血小板及中性粒细胞活化作用。结果与MI组相比,SAA可以改善MI小鼠的心功能及心脏病理变化;减少心肌组织中CD42c及外周血中CD62p的表达,同时不影响尾出血时间;降低ADP诱导的血小板活化,上调p-VASP/VASP比值,降低p-PI3K/PI3K和p-AKT/AKT比值;减少心肌组织中CD45、Ly6G以及CXCL1和CXCL2表达;减少心肌组织中补体成分C3aR的表达,降低C3a诱导的NE、MPO、MMP9、LF的水平。结论SAA具有通过抑制PI3K/AKT、VASP通路发挥抗血小板活化的作用,以及通过抑制C3aR及C3a的表达发挥抗中性粒细胞活化的作用。Aim To explore the effects of Salvianolic acid A(SAA)on platelet recruitment,activation and neutrophils in heart of myocardial infarction(MI)mice.Methods C57BL/6 mice were randomly divided into:Sham operation group,MI model group,SAA(5,10 mg·kg^(-1))group,tirofiban(Tirofiban,0.87 mg·kg^(-1))group,using tail vein injection for 3 d.Echocardiography and HE staining were used to detect mouse heart function and infarct area;IHC,FCS,ELISA,Western blot and other methods were used to explore the inhibitory effect of SAA on platelet and neutrophil activation.Results Compared with MI group,SAA could improve the cardiac function and cardiac physiology changes of MI mice,reduce the expression of CD42c in myocardial tissue and CD62p in peripheral blood without affecting tail bleeding time,reduce ADP-induced platelet activation and increase p-VASP/VASP ratio,reduce the ratio of p-PI3K/PI3K and p-AKT/AKT,reduce the expression of CD45,Ly6G,CXCL1 and CXCL2 in myocardial tissue,reduce the expression of complement component C3aR in myocardial tissue,and reduce C3a-induced NE and MPO,MMP9,LF level.Conclusions SAA has an anti-platelet activation effect by inhibiting the PI3K/AKT and VASP pathways and an anti-neutrophil activation effect by inhibiting the expression of C3aR and C3a.

关 键 词：丹酚酸A 心肌梗死 中性粒细胞 血小板募集 血小板活化 补体C3aR 

分 类 号：R-332[医药卫生] R284.1