复方丹参片和氯吡格雷联合使用对高血脂症小鼠血小板活化功能的影响

Effect of Fufang Danshen Tablets and Clopidogrel on Platelet Activation in Hyperlipidemic Mice

目的:观察复方丹参片和氢氯吡格雷联合使用对高血脂症小鼠血小板活化功能的影响,并探讨其分子机制。方法:健康昆明种小鼠50只,随机分为正常对照组、模型对照组、模型+氯吡格雷组(21 mg·kg-1.d-1)、模型+复方丹参片组(160 mg·kg-1.d-1)、模型+联合用药组(氯吡格雷21 mg·kg-1.d-1+复方丹参片160 mg·kg-1.d-1)5组,每组动物10只。ig给药2周后摘眼球采血,分离血清,测定各组小鼠血清总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,流式细胞仪检测各组小鼠的血小板活化功能。结果:氯吡格雷和复方丹参片对高血脂症小鼠的体重没有影响,氯吡格雷可显著降低高血脂症小鼠TC和LDL-C水平(P<0.05)。复方丹参片可显著降低高血脂症小鼠TC、TG和LDL-C水平(P<0.01或P<0.05)。高血脂症小鼠活化血小板比率(45.75±6.94)%,明显高于正常对照组(28.02±5.86)%,(P<0.01)。氯吡格雷均可显著降低高血脂症小鼠的活化血小板比率和中性粒细胞-血小板聚集率(P<0.01或P<0.05),复方丹参片可显著增强氯吡格雷降低高血脂症小鼠活化血小板比率、中性粒细胞-血小板聚集率和单核细胞-血小板聚集率的作用(25.19%±4.16%)vs(32.48%±4.74%);(8.64%±2.69%)vs(11.46%±2.33%);(20.12%±4.65%)vs(24.74%±4.67%),(P<0.01或P<0.05)。结论:高血脂症小鼠的血小板处于高活化状态,复方丹参片和氯吡格雷联合使用具有协同效应,复方丹参片能显著增强氯吡格雷抑制血小板活性的作用。

Objective： To study the effect of Fufang Danshen tablets and clopidogrel on the platelet activation in hyperlipidemic mice and its mechanism.Method： Fifty healthy Kunming mice were randomly divided into five groups： normal diet control group,high fat diet control group,clopidogrel gavage group,Fufang Danshen tablets gavage group and combined therapy gavage group.After administration of two weeks,the mice were killed and the blood samples were collected for the determination of serum total cholesterol（TC）,triglyceride（TG）,high-density lipoprotein cholesterol（HDL-C）,low-density lipoprotein cholesterol（LDL-C） and function of platelets.Result： Either clopidogrel or Fufang Danshen tablets had no effect on body weight in hyperlipidemic mice.Clopidogrel could significantly reduce the elevated TC and LDL-C of hyperlipidemic mice（P0.05）.Fufang Danshen tablets could significantly reduce the elevated TC,TG and LDL-C in hyperlipidemic mice（P0.05 or P0.01）.The activated platelets ratio（45.75±6.94）% in hyperlipidemic mice was significantly higher than that in control group（28.02±5.86）%（P0.01）.Clopidogrel could significantly reduce the elevated activated platelets ratio and neutrophil-platelet aggregation ratio in hyperlipidemic mice（P0.01）.Fufang Danshen tablets could significantly increase the inhibitory effect of clopidogrel on the elevated activated platelets ratio,neutrophil-platelet aggregation ratio and monocyte-platelet aggregation ratio in hyperlipidemic mice（25.19%±4.16%） vs（32.48%±4.74%）,（8.64%±2.69%） vs（11.46%±2.33%）,（20.12%±4.65%） vs（24.74%±4.67%）,（P0.01 or P0.05）.Conclusion： The platelet in hyperlipidemic mice is highly activated.The comnined clopidogrel and Fufang Danshen tablets have synergistic effect.Fufang Danshen tablets can significantly enchance the inhibitory effect of clopidogrel on function of platelets in hyperlipidemic mice.