Anti-Thrombotic Effect of a Novel Formula from Corni Fructus with Malic Acid, Succinic Acid and Citric Acid
Anti-Thrombotic Effect of a Novel Formula from Corni Fructus with Malic Acid, Succinic Acid and Citric Acid
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DOI：
10.1002/ptr.5052
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发表时间：
2014-05-01
影响因子：
7.2
通讯作者：
Bian, Hui-Min
中科院分区：
文献类型：
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作者：
Zhang, Qi-Chun;Zhao, Yue;Bian, Hui-Min
我们先前的研究已经证实了由苹果酸、琥珀酸和柠檬酸以3：2：2的比例组成的新的山茱萸果衍生配方对血小板聚集的抑制作用。本研究旨在进一步评价该方的体内抗血栓作用。采用小鼠急性肺血栓栓塞模型和大鼠动脉血栓形成模型，观察该方的抗血栓作用。HE染色观察内皮细胞形态学改变。测定大鼠血浆中TXB_2、6-K-PGF_（1）、cAMP、cGMP和NO的含量。体外测定ADP处理后血小板中IIb 3和ERK 1/2磷酸化水平。该配方显著降低了急性肺血栓栓塞症小鼠的恢复时间和死亡率。在大鼠中观察到该配方的显著延长的闭塞时间、降低的血栓重量和更多的整合的内皮。用该配方治疗的大鼠血浆中证实了6-K-PGF（1）、cGMP和NO的增加，但TXB 2和cAMP没有增加。最后，该配方显示抑制血小板中IIb 3表达和ERK 1/2活化。该配方显示出积极的抗血栓形成作用。直接干扰血小板ADP激活信号和调节内皮功能是其抗血栓作用的两条主要途径。版权所有（c）2013约翰威利父子有限公司
Our previous investigation had confirmed the inhibition of platelet aggregation of a novel Corni fructus-derived formula composed of malic acid, succinic acid and citric acid with a ratio of 3:2:2. The present study was to further evaluate the anti-thrombotic effect of the formula in vivo. Mice of acute pulmonary thromboembolism, and rats of arterial thrombosis were used to determine the anti-thrombotic effect of the formula. Histology analysis of endothelium was conducted with hematoxylin and eosin stain. TXB2, 6-K-PGF(1), cAMP, cGMP and NO in rat plasma were determined. In vitro assay of IIb3 and phosphorylation of ERK1/2 were performed in ADP-treated platelet. The formula significantly reduced the recovery time and mortality rate of mice with acute pulmonary thromboembolism. Remarkably extended occlusion time, decreased thrombus weight and more integrated endothelium were observed in rat with the formula. Enhanced 6-K-PGF(1), cGMP and NO, but not TXB2 and cAMP, were demonstrated in rat plasma with treatment of the formula. Finally, the formula was shown to inhibit IIb3 expression and activation of ERK1/2 in platelet. The formula shows positive anti-thrombotic effect. The direct interference on ADP activated signaling in platelet and regulation of endothelium function are two primary pathways involved in the action on thrombosis. Copyright (c) 2013 John Wiley & Sons, Ltd.