BACKGROUND Tanshinone IIA (TS IIA), a multi-pharmaceutical compound from traditional Chinese herb, is effective for treatment of atherothrombosis. However, the underlying mechanisms of TS IIA-mediated anti-platelet activation effect are still poorly understood. As shown in our previous study, platelet-derived microvesicles (PMVs) generated in response to oxidant insult could activate CD36/mitogen-activated protein kinase kinase 4/Jun N-terminal kinase 2 (CD36/MKK4/JNK2) signals and lead to platelet activation. The present study aims to investigate the effect of TS IIA on platelet activation and the possible mechanisms. METHODS The production of PMVs induced by Interleukin 6 (IL-6) was detected by flow cytometry. We performed activating studies of platelets with PMVs derived from IL-6-treated platelets (IL-6-PMVs) in vitro. Sometimes, platelet suspensions were incubated with serial concentrations of TS IIA for 15 min before being stimulated with IL-6-PMVs. Expression of platelet integrin αIIbβ3 and CD36 was detected by flow cytometry. Phosphorylation of MKK4 and JNK were detected by immunoblotting. RESULTS Here we demonstrated firstly that TS IIA could prevent platelet activation induced by PMVs and down-regulates CD36 and MKK4/JNK2 signaling pathway. CD36 may be the target of atherosclerosis (AS)-related thrombosis. CONCLUSIONS This study showed the possible mechanisms of TS IIA-mediated anti-platelet activation and may provide a new strategy for the treatment of AS-related thrombosis by targeting platelet CD36.

中文翻译：

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丹参酮IIA阻止血小板活化并下调CD36和MKK4 / JNK2信号通路。

背景技术丹参酮IIA（TS IIA）是一种来自传统中草药的多药物化合物，可有效治疗动脉粥样硬化。然而，TS IIA介导的抗血小板活化作用的潜在机制仍知之甚少。如我们先前的研究所示，对氧化剂的损害而产生的血小板衍生的微囊泡（PMV）可以激活CD36 /丝裂原活化的蛋白激酶激酶4 / Jun N端激酶2（CD36 / MKK4 / JNK2）信号并导致血小板激活。本研究旨在研究TS IIA对血小板活化的影响及其可能的机制。方法采用流式细胞仪检测白介素6（IL-6）诱导的PMV的产生。我们在体外用源自IL-6处理的血小板（IL-6-PMV）的PMV进行了血小板活化研究。有时，将血小板悬浮液与系列浓度的TS IIA孵育15分钟，然后再用IL-6-PMV刺激。通过流式细胞术检测血小板整合素αIIbβ3和CD36的表达。通过免疫印迹检测到MKK4和JNK的磷酸化。结果在此我们首先证明TS IIA可以预防由PMV诱导的血小板活化并下调CD36和MKK4 / JNK2信号通路。CD36可能是与动脉粥样硬化（AS）相关的血栓形成的靶标。结论这项研究显示了TS IIA介导的抗血小板活化的可能机制，并且可能通过靶向血小板CD36为AS相关性血栓形成提供了新的策略。流式细胞术检测血小板整合素αIIbβ3和CD36的表达。通过免疫印迹检测到MKK4和JNK的磷酸化。结果在此我们首先证明TS IIA可以预防由PMV诱导的血小板活化并下调CD36和MKK4 / JNK2信号通路。CD36可能是与动脉粥样硬化（AS）相关的血栓形成的靶标。结论这项研究显示了TS IIA介导的抗血小板活化的可能机制，并且可能通过靶向血小板CD36为AS相关性血栓形成提供了新的策略。通过流式细胞术检测血小板整合素αIIbβ3和CD36的表达。通过免疫印迹检测到MKK4和JNK的磷酸化。结果在此我们首先证明TS IIA可以预防由PMV诱导的血小板活化并下调CD36和MKK4 / JNK2信号通路。CD36可能是与动脉粥样硬化（AS）相关的血栓形成的靶标。结论这项研究显示了TS IIA介导的抗血小板活化的可能机制，并且可能通过靶向血小板CD36为AS相关性血栓形成提供了新的策略。CD36可能是与动脉粥样硬化（AS）相关的血栓形成的靶标。结论这项研究显示了TS IIA介导的抗血小板活化的可能机制，并且可能通过靶向血小板CD36为AS相关性血栓形成提供了新的策略。CD36可能是与动脉粥样硬化（AS）相关的血栓形成的靶标。结论这项研究显示了TS IIA介导的抗血小板活化的可能机制，并且可能通过靶向血小板CD36为AS相关性血栓形成提供了新的策略。