期刊
THROMBOSIS RESEARCH
卷 133, 期 4, 页码 610-615出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2014.01.029
关键词
MC-002; Platelet aggregation; TXA(2); Inflammation
资金
- National Science & Technology Major Project [2012ZX09102101-005]
- Qing Lan Project
- 333 project
Introduction: Thromboxane A(2) (TXA(2)) induces platelet aggregation and vasoconstriction, and agents that inhibit TXA(2) production or interaction with receptors may exert potential application in stroke therapy. Aim: To illustrate the platelet aggregation antagonistic and endothelial protective effect of (E) - 3 - (3 - methoxy 4 - ((3, 5, 6 - trimethylpyrazin - 2 - yl) methoxy) phenyl) sodium acrylate (MC-002) through TXA(2) inhibition and underline mechanisms. Materials and methods: Platelets aggregation and thoracic aorta ring contraction of rabbits were induced by U46619. Human umbilical vein endothelial cells (HUVECs) were further applied to explore the protective effect of MC-002 on endothelium when exposed to tumor necrosis factor - alpha (TNF-alpha). MTT method was used to assess cell damage, and ELISA analysis was exerted to estimate nitrogen monoxide (NO), endothelin-1 (ET-1), thromboxane B-2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) releasing. Fluorescence spectrophotometry was conducted to determine intracellular calcium concentration ([Ca2+](i)), and western blotting method was applied to evaluate the protein expressions of intracellular adhesion molecule-1 (ICAM-1), P-selectin and nuclear factor-kappa B (NF-kappa B). Results and conclusions: TXA(2) analog U46619 mediated obvious platelet aggregation and vasoconstriction. MC-002 inhibited platelet aggregation through administration in vivo and incubation with platelet in vitro, and relaxed aorta ring in endothelium dependent manner. MC-002 alleviated cell damage, [Ca2+] i overload, ET-1 overexcretion and TXB2 activation, but improved NO availability reduction in HUVECs treated with TNF-alpha. Furthermore, MC-002 downregulated ICAM-1, P-selectin and NF-kappa B overexpression induced by TNF-alpha. In conclusion, MC-002 exerted antiplatelet aggregation effect through TXA(2) inhibition and relieved inflammatory injury of endothelial cells through NF-kappa B signal pathway. (C) 2014 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据