剪应力联合丹参山楂提取物抗血栓作用机制的研究

中国药物警戒 ›› 2018, Vol. 15 ›› Issue (8): 462-466.

• 生物力药理学研究专栏 • 上一篇下一篇

剪应力联合丹参山楂提取物抗血栓作用机制的研究

王薇¹, 贡磊磊², 李丽², 王岚², 殷小杰², 梁日欣^{2 *}, 廖福龙²

¹首都医科大学中医药学院,北京 100069;
²中国中医科学院中药研究所,北京 100700

收稿日期:2018-10-11 修回日期:2018-10-11 出版日期:2018-08-20 发布日期:2018-10-11
作者简介:王薇,女,硕士,中药心血管药理。
基金资助:
国家自然科学基金（81473548）：活血化瘀抗动脉粥样硬化与血栓形成的剪应力效应机理

Study on the Antithrombotic Mechanism of Joint of Shear Stress with the Fruit of Crataegus Pinnatifida Bge. Var. majar N.E. Br. and the Root of Salviae Miltiorrhizae Bge

WANG Wei¹, GONG Leilei², LI Li², WANG Lan², YIN Xiaojie², LIANG Rixin^2*, LIAO Fulong²

¹School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China;
²Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

Received:2018-10-11 Revised:2018-10-11 Online:2018-08-20 Published:2018-10-11

摘要/Abstract

摘要： 目的研究流动剪应力与活血化瘀药物丹参山楂提取物联合应用抗血栓的作用机制。方法采用生物力药理学的研究方法,利用BioFlux1000控剪应力微流培养系统,分别施加0.1、0.9 Pa剪应力并联合不同剂量丹参山楂提取物对血管内皮细胞（HUVECs）进行预处理后,用ox-LDL诱导内皮细胞损伤,采用酶联免疫吸附法（ELISA）检测细胞上清液中PAI-1、t-PA、ICAM-1的含量;采用RT-PCR法分别测定PAI-1、t-PA、ICAM-1基因表达。结果丹参山楂提取物能下调内皮细胞中PAI-1 mRNA的相对表达,减少内皮细胞中PAI-1的分泌;与低剪应力相比,正常剪应力联合大剂量丹参山楂提取物能够上调内皮细胞中t-PA mRNA的表达,增加内皮细胞分泌t-PA;在低剪应力条件下,丹参山楂提取物可明显抑制ICAM-1的表达。结论正常水平剪应力联合丹参山楂提取物能够通过调节纤溶系统的稳定性来抑制血栓形成;丹参山楂提取物能够通过抑制内皮细胞中PAI-1 的表达产生抗血栓效应;在病理剪应力条件下,丹参山楂提取物对抑制ICAM-1表达的药效更加显著。

关键词: 剪应力, 丹参山楂提取物, 血管内皮细胞, 抗血栓

Abstract: Objective To investigate the joint effects of flow shear stress and blood-activiating and stasis-dissolving drugs the fruit of Crataegus Pinnatifida Bge. Var. majar N.E. Br.(CP) and the root of Salviae Miltiorrhizae Bge(SM) on the expression of PAI-1, t-PA and ICAM-1 in endothelial cells damaged by OX-LDL and its possible antithrombotic mechanisms. Methods By using Bioflux 1000 microfluidic system, shear stresses of 0.1 Pa and 0.9 Pa were applied together with different doses of the fruit of CP and the root of SM treatment on human vascular endothelial cells (HUVECs) damaged by OX-LDL, then the cell supernatant was collected to detect concentration of PAI-1,t-PA and ICAM-1 by ELISA, the mRNA expressions of PAI-1,t-PA and ICAM-1 in cells were detected by RT-PCR. Results Compared with the model group, the contents of PAI-1 mRNA expressions were lower after treated with the fruit of CP and the root of SM and reduced the secretion of PAI-1 in cells supernatant. Physical shear stress of 0.9 Pa combined with the fruit of CP and the root of SM could significantly promote the endothelial secretion of t-PA and the contents of t-PA mRNA expressions were increased. The contents of ICAM-1 expressions were lower after treated with the fruit of CP and the root of SM in low shear stress condition. Conclusion The fruit of CP and the root of SM can inhibit thrombosis by inhibiting the expression of PAI-1 in endothelial cells. Physical shear stress and the fruit of CP and the root of SM can inhibit thrombosis by regulating the stability of the fibrinolytic system; low shear stress may influence the fruit of CP and the root of SM antithrombotic effect through downregulation of ICAM-1.

Key words: shear stress, the fruit of Crataegus Pinnatifida Bge. Var. majar N.E. Br. and the root of Salviae Miltiorrhizae Bge, endothelial cells, antithrombosis

中图分类号:

R965

王薇, 贡磊磊, 李丽, 王岚, 殷小杰, 梁日欣, 廖福龙. 剪应力联合丹参山楂提取物抗血栓作用机制的研究[J]. 中国药物警戒, 2018, 15(8): 462-466.

WANG Wei, GONG Leilei, LI Li, WANG Lan, YIN Xiaojie, LIANG Rixin, LIAO Fulong. Study on the Antithrombotic Mechanism of Joint of Shear Stress with the Fruit of Crataegus Pinnatifida Bge. Var. majar N.E. Br. and the Root of Salviae Miltiorrhizae Bge[J]. Chinese Journal of Pharmacovigilance, 2018, 15(8): 462-466.

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剪应力联合丹参山楂提取物抗血栓作用机制的研究

Study on the Antithrombotic Mechanism of Joint of Shear Stress with the Fruit of Crataegus Pinnatifida Bge. Var. majar N.E. Br. and the Root of Salviae Miltiorrhizae Bge

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