流动条件下血栓通胶囊抗血小板黏附的分子药理学机制研究.docVIP

流动条件下血栓通胶囊抗血小板黏附的分子药理学机制研究 　　[摘要]研究流?犹跫?下血栓通胶囊（XST）抗血小板黏附的效应及其可能的作用机制。利用BioFlux 1000控剪应力微流培养系统模拟体内流动条件，建立TNFα诱导的血管内皮细胞损伤模型，动态实时观察XST（03 g?L1）对血小板黏附于受损血管内皮细胞表面的影响。以Western blotting法测定血管内皮细胞VCAM1的表达，以放射免疫法检测6ketoPGF1α，TXB2的分泌。结果显示，生理和病理流动条件下XST均可抑制血小板黏附，抑制率分别为150%，341%；在病理低剪应力或静态条件下，XST能够明显抑制血管内皮细胞VCAM1的表达和TXB2释放（P005）。该研究从血流/血管/血液相互作用的角度发现，XST可能通过内皮细胞保护途径，抑制血小板黏附，进而发挥其抗血栓形成的效应。在不同流动条件下，XST抗血小板黏附的效应有所不同，病理低剪应力更有利于XST药效的发挥。 　　[关键词]剪应力； 血栓通胶囊； 血管内皮细胞； 血小板 　　Antiplatelet adhesive effect and mechanisms of Xueshuantong 　　capsules under flow conditions 　　HAN Shuxian1， CHEN Ying1， ZHANG Qian1， HAN Bing2， GE Yimeng2， XIANG Yanhua2， LIAO Fulong1， YOU Yun1* 　　（1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Science， Beijing 100700， China； 　　2. Harbin Zhenbao Pharmaceutical Co.， Ltd.， Harbin 150060， China） 　　[Abstract]To investigate the antiplatelet adhesive effect and possible mechanisms of Xueshuantong capsule （XST） under flow conditions Human umbilical vein endothelial cells （HUVECs） and human platelets were employed as experimental materials， and TNFα （20 μg?L-1） was used to establish vascular endothelial cell injury models In vivo flow conditions were simulated under controlled shear stress of 01 Pa and 09 Pa by Bioflux1000 assays accordingly Antiplatelet adhesive effects of XST at 03 g?L1 were dynamically monitored by microscopic timelapse photography Western blotting was employed to detect the VCAM1 expression on endothelial cells， and the release of 6ketoPGF1α and TXB2 was tested by radioimmunoassay The results showed that XST could inhibit the platelets adhesion under both physiological and pathological flow conditions， and the inhibition rate was 150% and 341% respectively Under pathological low shear stress or static conditions， XST could significantly inhibit endothelial cells VCAM1 expression and TXB2 release （P005） These results suggested that XST inhibited platelets adhering to injured endothelium via decreasing VCAM1 expression an