Han Shu-Xian, Chen Ying, Zhang Qian, Han Bing, Ge Yi-Meng, Xiang Yan-Hua, Liao Fu-Long, You Yun
Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing 100700, China.
Harbin Zhenbao Pharmaceutical Co., Ltd., Harbin 150060, China.
Zhongguo Zhong Yao Za Zhi. 2017 Jan;42(2):341-346. doi: 10.19540/j.cnki.cjcmm.20161222.014.
To investigate the anti-platelet 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 TNF-α (20 μg•L⁻¹) was used to establish vascular endothelial cell injury models. In vivo flow conditions were simulated under controlled shear stress of 0.1 Pa and 0.9 Pa by Bioflux1000 assays accordingly. Anti-platelet adhesive effects of XST at 0.3 g•L⁻¹ were dynamically monitored by microscopic time-lapse photography. Western blotting was employed to detect the VCAM-1 expression on endothelial cells, and the release of 6-keto-PGF1α 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 15.0% and 34.1% respectively. Under pathological low shear stress or static conditions, XST could significantly inhibit endothelial cells VCAM-1 expression and TXB2 release (P<0.05). These results suggested that XST inhibited platelets adhering to injured endothelium via decreasing VCAM-1 expression and TXA2 secretion from endothelium. From the interactions among blood flow, vascular endothelium and platelets, the anti-thrombosis effects of XST were possibly related to endothelial cells protection and therefore inhibiting platelets adhesion. Under different flow conditions, the antiplatelet adhesion effect of XST was different, and the pathological low shear stress was more conducive to the efficacy of XST.
探讨血栓通胶囊(XST)在流动条件下的抗血小板黏附作用及可能机制。以人脐静脉内皮细胞(HUVECs)和人血小板为实验材料,用肿瘤坏死因子-α(TNF-α,20μg•L⁻¹)建立血管内皮细胞损伤模型。通过Bioflux1000检测法在0.1Pa和0.9Pa的控制剪切应力下模拟体内流动条件。采用显微延时摄影动态监测0.3g•L⁻¹ XST的抗血小板黏附作用。用蛋白质免疫印迹法检测内皮细胞上血管细胞黏附分子-1(VCAM-1)的表达,用放射免疫分析法检测6-酮-前列腺素F1α(6-keto-PGF1α)和血栓素B2(TXB2)的释放。结果表明,XST在生理和病理流动条件下均能抑制血小板黏附,抑制率分别为15.0%和34.1%。在病理低剪切应力或静态条件下,XST能显著抑制内皮细胞VCAM-1表达和TXB2释放(P<0.05)。这些结果提示,XST通过降低内皮细胞VCAM-1表达和TXA2分泌来抑制血小板黏附于受损内皮。从血流、血管内皮和血小板之间的相互作用来看,XST的抗血栓作用可能与保护内皮细胞从而抑制血小板黏附有关。在不同流动条件下,XST的抗血小板黏附作用不同,病理低剪切应力更有利于XST发挥药效。