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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 observe the effect of compound Danshen Tablets and hydrochloropiridogrel on platelet activation in mice with hyperlipidemia and to explore its molecular mechanism. Methods: Fifty healthy Kunming mice were randomly divided into normal control group, model control group, model + clopidogrel group (21 mg · kg-1.d-1), model group + Danshen Tablet group kg-1.d-1), model group + combination group (clopidogrel 21 mg · kg-1.d-1 + compound Danshen tablets 160 mg · kg-1.d-1) only. After 2 weeks of administration, blood was collected from the eyes and the serum was separated. The levels of TC, TG, HDL-C, LDL -C) levels, flow cytometry platelet activation in each group of mice. Results: Clopidogrel and Fufang Danshen Tablets had no effect on the body weight of hyperlipidemic mice. Clopidogrel significantly reduced the levels of TC and LDL-C in hyperlipidemic mice (P <0.05). Compound Danshen Tablet can significantly reduce hyperlipidemia mice TC, TG and LDL-C levels (P <0.01 or P <0.05). The percentage of activated platelets in hyperlipidemic mice was (45.75 ± 6.94)%, which was significantly higher than that in normal controls (28.02 ± 5.86)% (P <0.01). Clopidogrel can significantly reduce the activated platelet ratio and neutrophil - platelet aggregation rate in hyperlipidemic mice (P <0.01 or P <0.05), and the compound salvia miltiorrhiza tablet can significantly reduce clopidogrel in mice with hyperlipidemia (25.19% ± 4.16%) vs (32.48% ± 4.74%); (8.64% ± 2.69%) vs (11.46% ±%) effects of activated platelet, neutrophil-platelet aggregation and monocyte-platelet aggregation 2.33%); (20.12% ± 4.65%) vs (24.74% ± 4.67%) (P <0.01 or P <0.05). CONCLUSION: The platelet of hyperlipidemic mice is in a highly activated state. The combination of compound Salviae miltiorrhizae and clopidogrel has a synergistic effect. Compound Salvia miltiorrhiza tablet can significantly enhance the inhibitory effect of clopidogrel on platelet activity.