Clopidogrel reduces lipopolysaccharide-induced inflammation and neutrophil-platelet aggregates in an experimental endotoxemic model
Clopidogrel reduces lipopolysaccharide-induced inflammation and neutrophil-platelet aggregates in an experimental endotoxemic model
复制标题
在实验性内毒素血症模型中，氯吡格雷可减少脂多糖诱导的炎症和中性粒细胞血小板聚集
DOI：
10.1002/jbt.22279
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发表时间：
2019-04-01
影响因子：
3.6
通讯作者：
Xiao, Xian-Zhong
中科院分区：
文献类型：
--
作者：
Wang, Xiao-Li;Deng, Hua-Fei;Xiao, Xian-Zhong
血小板活化有助于炎症中的器官衰竭，并在内毒素血症中起重要作用。氯吡格雷抑制血小板聚集和活化。然而，氯吡格雷在调节内毒素血症炎症进展中的作用在很大程度上仍未被探索。因此，我们研究了氯吡格雷在脂多糖（LPS）诱导的小鼠炎症中对血小板和白细胞活化的作用。动物在LPS诱导前用氯吡格雷或载药。测定中性粒细胞-血小板聚集物的表达、血小板活化和组织因子的表达。免疫荧光法分析血小板-白细胞相互作用及白细胞组织因子（TF）表达。氯吡格雷预处理可显著减轻肺损伤，抑制血小板-中性粒细胞聚集和TF表达。此外，氯吡格雷还能减少内毒素血症小鼠的血小板减少，并影响循环白细胞的数量。此外，氯吡格雷还能降低内毒素小鼠血小板中CD40L和CD62P的脱落。综上所述，氯吡格雷在内毒素血症中通过降低血小板活化和炎症过程发挥重要作用。
Platelet activation contributes to organs failure in inflammation and plays an important role in endotoxemia. Clopidogrel inhibits platelet aggregation and activation. However, the role of clopidogrel in modulating inflammatory progression of endotoxemia remains largely unexplored. Therefore, we investigated the role of clopidogrel on the activation of platelet and leukocytes in lipopolysaccharide (LPS)-induced inflammation in mice. Animals were treated with clopidogrel or vehicle before LPS induction. The expression of neutrophil-platelet aggregates and platelet activation and tissue factor was determined. Immunofluorescence was used to analyze platelet-leukocyte interactions and tissue factor (TF) expression on leukocytes. Clopidogrel pretreatment markedly decreased lung damage, inhibited platelet-neutrophil aggregates and TF expression. In addition, clopidogrel reduced thrombocytopenia and affected the number of circulating white blood cell in endotoxemia mice. Moreover, clopidogrel also reduced platelet shedding of CD40L and CD62P in endotoxemic mice. Taken together, clopidogrel played an important role through reducing platelet activation and inflammatory process in endotoxemia.