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丹参素对血小板聚集和血栓形成的影响:大鼠体内动静脉分流和静脉血栓形成模型

Effects of danshensu on platelet aggregation and thrombosis: in vivo arteriovenous shunt and venous thrombosis models in rats.

作者信息

Yu Chen, Qi Dong, Lian Wei, Li Qing-Zhong, Li Hong-Juan, Fan Hua-Ying

机构信息

School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.

Department of Nephrology, Yantai Yu-Huang-Ding/Qingdao University Hospital, Yantai, Shandong, China.

出版信息

PLoS One. 2014 Nov 6;9(11):e110124. doi: 10.1371/journal.pone.0110124. eCollection 2014.

Abstract

Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)--widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated thromboxane B2 (TXB2) and up regulated 6-keto prostaglandin F1α (6-keto-PGF1α), normalizing the TXB2/6-keto-PGF1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A2(TXA2)/prostacyclin(PGI2) balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.

摘要

丹参素是一种二羟基苯乳酸,是唇形科植物丹参(一种广泛使用的传统中药)干燥根中含量最丰富的活性酚酸之一。采用多种方法研究了丹参素对大鼠血小板聚集和血栓形成的影响。结果发现,丹参素在2种实验性血栓形成模型中显著降低血栓重量;在正常大鼠和血瘀模型大鼠中,对二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集呈剂量依赖性抑制;丹参素还显著降低血液黏度、血浆黏度和血细胞比容水平。此外,丹参素显著抑制静脉血栓形成诱导的静脉壁中环氧合酶-2(COX-2)而非环氧合酶-1(COX-1)的表达,下调血栓素B2(TXB2)并上调6-酮前列腺素F1α(6-keto-PGF1α),使TXB2/6-keto-PGF1α比值正常化。此外,丹参素不会引起胃部病变,甚至在高达60mg/kg的剂量下对阿司匹林诱导的溃疡形成具有保护作用。这些发现表明,丹参素的抗血栓和抗血小板聚集作用归因于其对COX-2的高度选择性抑制以及使血栓素A2(TXA2)/前列环素(PGI2)平衡正常化的能力。这些发现表明,丹参素在抗血栓和抗血小板治疗方面具有广阔的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee70/4222847/bce9ed14fe6c/pone.0110124.g001.jpg

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