Pediatrics, University of Alberta, Edmonton, AB, Canada.
J Ethnopharmacol. 2011 Sep 1;137(1):44-9. doi: 10.1016/j.jep.2011.03.047. Epub 2011 Mar 29.
Tanshinone IIA (STS), an active ingredient of the Chinese herb Danshen (Salvia miltiorrhiza) for angina and stroke in adults, has been reported to inhibit platelet function. However, its effect on platelet and underlying mechanism remain largely unknown, particularly in neonates.
To investigate the effect of STS on the platelet aggregation and its interaction with various platelet activation pathways, platelet aggregatory function was studied in whole blood stimulated by collagen (2-10 μg/ml) ex vivo in newborn piglets receiving intravenous STS (0.1-10mg/kg, n=8) and in vitro in whole blood from newborn piglets (n=6) incubated with STS (0.1-100 μg/ml). The respective morphological changes of platelets were also examined by scanning electron microscopy. Plasma levels of nitrite/nitrate (NOx) and thromboxane B(2) (TxB(2)), matrix metalloproteinase (MMP)-2 and -9 activities were also examined. To further delineate the mechanistic pathway, the effect of STS on endothelial microparticles release from cultured human umbilical vein endothelial cells (HUVECs) was quantified by flow cytometry.
STS impaired the ex vivo, but not in vitro, collagen-stimulated platelet aggregation. Infusion of STS elevated the plasma level of TxB(2) at 10mg/kg. However, STS had no effect on NOx level. Incubating cultured HUVECs with STS (1 and 10 μg/ml) caused a significant release of endothelial microparticles. Morphologically, STS elicited platelet activation in vivo, but not in vitro.
STS impairs the ex vivo whole blood platelet aggregatory function by activating platelet in vivo in healthy newborn piglets. It implies that STS may elicit its effects by stimulating endothelial microparticles production and eicosanoid metabolism pathway.
丹参酮 IIA（STS）是中国草药丹参治疗成人心绞痛和中风的一种有效成分，据报道它可以抑制血小板功能。然而，其对血小板的作用及其潜在机制在很大程度上尚不清楚，特别是在新生儿中。
为了研究 STS 对血小板聚集的影响及其与各种血小板激活途径的相互作用，本研究在接受静脉内 STS（0.1-10mg/kg，n=8）的新生仔猪的体外全血中，以及在新生仔猪（n=6）的体外全血中，研究了 STS（0.1-100μg/ml）刺激下的血小板聚集功能。还通过扫描电子显微镜检查了血小板的形态变化。还检查了血浆中亚硝酸盐/硝酸盐（NOx）和血栓素 B（2）（TxB（2））、基质金属蛋白酶（MMP）-2 和 -9 活性的水平。为了进一步阐明机制途径，通过流式细胞术定量测定 STS 对培养的人脐静脉内皮细胞（HUVECs）释放的内皮微颗粒的影响。
STS 损害了体外而非体外胶原刺激的血小板聚集。STS 输注在 10mg/kg 时升高了 TxB（2）的血浆水平。然而，STS 对 NOx 水平没有影响。用 STS（1 和 10μg/ml）孵育培养的 HUVECs 会导致内皮微颗粒的显著释放。形态学上，STS 在体内引起血小板激活，但在体外没有。
STS 通过在健康新生仔猪体内激活血小板，损害了体外全血血小板聚集功能。这表明 STS 可能通过刺激内皮微颗粒产生和类花生酸代谢途径发挥其作用。
