中国全科医学Issue(3)：283-287,5.DOI:10.3969/j.issn.1007-9572.2015.03.011
阿司匹林和氯吡格雷对体外血小板黏附内皮细胞基质活性的影响及其机制研究
Ettects ot Aspirin and Clopidogrel on the Adhesion Activity ot Platelet to Endothelial Cell Matrix in Vitro and Its Mechanism
摘要
Abstract
Objective To study the effects of aspirin and clopidogrel on the adhesion activity of platelet to endothelial cell matrix in vitro and its mechanism, and to find the reasons why combination use of two drugs is better than monotherapy. Methods A total of 42 healthy female SD rats were bought from the animal centre of Third Military Medical University. By using random number table method,SD rats were divided into aspirin group(8 rats),clopidogrel group(8 rats),aspirin and clopidogrel(combination)group(8 rats),control group(8 rats),the other 10 rats were used for primary isolation and culture of cells. The isolated and cultured primary rat vascular endothelial cells were treated with ox - LDL to establish damaged vascular endothelial cell model. 100 mg/ kg aspirin,10 mg/ kg clopidogrel,combination of 100 mg/ kg aspirin and 10 mg/ kg clopidogrel,and 200 μl castor oil were used respectively to prepare endothelial cell matrix plate. 3 days before the separation and preparation of platelet from plasma,rats in aspirin group were fed with 100 mg·kg - 1 ·d - 1 aspirin,rats in clopidogrel group were fed with 10 mg·kg - 1 ·d - 1 clopidogrel,rats in aspirin and clopidogrel group were fed with 100 mg·kg - 1 ·d - 1 aspirin and 10 mg·kg - 1 ·d - 1 clopidogrel,rats in control group were fed with castor oil 200 μl per day. ELISA assay was used to evaluate the amount of platelets which adhered to the endothelial matrix. Western blotting technology was used to evaluate the effects of aspirin and clopidogrel on expression of thrombomodulin(TM),lectin like oxidized low density lipoprotein receptor- 1(LOX - 1)and CD40 in vascular endothelial cells. Results The adhesion activity of aspirin/ clopidogrel - treated platelet to endothelial cell matrix:there were significant differences in adhesion activity of aspirin/ clopidogrel - treated(50,100,150, 200 μl)platelet to endothelial cell matrix among 4 groups(P ﹤ 0. 05),adhesion activity of aspirin/ clopidogrel - treated platelet to endothelial cell matrix in clopidogrel group and combination group was significantly lower than that in control group and aspirin group,respectively,adhesion activity of aspirin/ clopidogrel - treated(150 μl) platelet to endothelial cell matrix in aspirin group was significantly lower than that in control group(P ﹤ 0. 05). The adhesion activity of platelet to aspirin/ clopidogrel -treated endothelial cell matrix:there were significant differences in adhesion activity of platelet to aspirin/ clopidogrel - treated (50,100,150,200 μl) endothelial cell matrix among 4 groups( P ﹤ 0. 05 ),adhesion activity of platelet to aspirin/clopidogrel - treated(50,100,150,200 μl)endothelial cell matrix in combination group was significantly lower than that in control group,aspirin group,clopidogrel group,respectively(P ﹤ 0. 05). According to western blotting results,both aspirin and clopidogrel could inhibit ox - LDL - induced decreasing expression of TM. Ox - LDL could induce LOX - 1 expression in vascular endothelial cells,aspirin could inhibit ox - LDL - induced expression of LOX - 1 and IL - 6 obviously,clopidogrel could inhibit CD40 expression in endothelial cells obviously. Conclusion Both aspirin and clopidogrel can reduce adhesion activity of platelet to endothelial cell matrix through increasing TM level and inhibiting inflammatory factors. The combination use of the two drugs can inhibit ox - LDL - induced expression of inflammatory cytokines obviously,and reduce the adhension of platelet to endothelial cell matrix.关键词
氯吡格雷/阿司匹林/血小板/内皮细胞基质Key words
Clopidogrel/Aspirin/Blood platelets/Endothelial cell matrix分类
医药卫生引用本文复制引用
朱晋坤,毛华,尹扬光,董文,杜峰,鲁玉明,熊宗华,邓梦扬..阿司匹林和氯吡格雷对体外血小板黏附内皮细胞基质活性的影响及其机制研究[J].中国全科医学,2015,(3):283-287,5.基金项目
贵州省科技厅社会发展项目 （）
