王海港, 孔令雷, 王睿, 陈燕霞, 杨时伦, 赵晓悦, 周启蒙, 杜冠华. 丹酚酸A与阿司匹林抗血栓作用的比较研究J. 药学学报, 2019,54(2): 301-307. doi: 10.16438/j.0513-4870.2018-0895
引用本文: 王海港, 孔令雷, 王睿, 陈燕霞, 杨时伦, 赵晓悦, 周启蒙, 杜冠华. 丹酚酸A与阿司匹林抗血栓作用的比较研究J. 药学学报, 2019,54(2): 301-307. doi: 10.16438/j.0513-4870.2018-0895
WANG Hai-gang, KONG Ling-lei, WANG Rui, CHEN Yan-xia, YANG Shi-lun, ZHAO Xiao-yue, ZHOU Qi-meng, DU Guan-hua. Comparison of antithrombotic effects between salvianolic acid A and aspirinJ. Acta Pharmaceutica Sinica, 2019,54(2): 301-307. doi: 10.16438/j.0513-4870.2018-0895
Citation: WANG Hai-gang, KONG Ling-lei, WANG Rui, CHEN Yan-xia, YANG Shi-lun, ZHAO Xiao-yue, ZHOU Qi-meng, DU Guan-hua. Comparison of antithrombotic effects between salvianolic acid A and aspirinJ. Acta Pharmaceutica Sinica, 2019,54(2): 301-307. doi: 10.16438/j.0513-4870.2018-0895

丹酚酸A与阿司匹林抗血栓作用的比较研究

Comparison of antithrombotic effects between salvianolic acid A and aspirin

  • 摘要: 阿司匹林(aspirin,ASP)和丹酚酸A(salvianolic acid A,SAA)均为抗血小板、抑制血栓形成的化合物,为了探讨二者的作用特点,本研究考察了丹酚酸A和阿司匹林在大鼠体内外抗血小板聚集作用,同时在血栓性脑缺血模型大鼠中,考察丹酚酸A和阿司匹林的抗血小板聚集及抗脑缺血作用,比较丹酚酸A和阿司匹林抗血栓作用的特点。动物福利和实验过程均遵循中国医学科学院动物伦理委员会的规定。体内外抗血小板聚集实验结果显示,丹酚酸A能够剂量依赖性地抑制二磷酸腺苷(adenosine diphosphate,ADP)、花生四烯酸(arachidonic acid,AA)和凝血酶(thrombin,THR)诱导的血小板聚集,阿司匹林在体内实验中对AA诱导的血小板聚集具有较强的抑制作用;丹酚酸A和阿司匹林对正常凝血系统的作用类似。在脑缺血大鼠模型中的血小板最大聚集率(maximum platelet aggregation rate,MAR)显示,相比于模型组MARADP=(41.67±4.55)%,MARAA=(53.22±2.83)%,MARTHR=(73.33±5.04)%,丹酚酸A显著抑制ADP和AAMARADP=(26.13±4.60)%,MARAA=(35.53±13.73)%诱导的血小板聚集(P<0.01),而阿司匹林对AAMARAA=(8.13±2.99)%诱导的血小板聚集作用较强;脑缺血模型组大鼠的脑梗死体积为(43.50±12.69)%和脑含水量为(82.25±0.89)%,丹酚酸A(10 mg·kg-1)(10.77±7.80)%和(79.72±0.83)%均有改善作用(P<0.01),而阿司匹林(100 mg·kg-1)未见明显作用。以上结果表明,与阿司匹林相比,丹酚酸A不仅对血小板聚集具有全面温和的抑制作用,而且对血栓引起的脑缺血具有显著的保护作用。因此,丹酚酸A对血栓性疾病的预防和治疗将具有良好的应用前景。

     

    Abstract: This study was designed to compare the antithrombotic effects of salvianolic acid A and aspirin. The anti-platelet aggregation and anticoagulant effects of salvianolic acid A and aspirin in vitro and in vivo were investigated in normal rats. The anti-cerebral ischemia and anti-platelet aggregation effects of salvianolic acid A and aspirin were also investigated in rats with thrombotic cerebral ischemia. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. The results of antiplatelet aggregation in vitro and in vivo showed that salvianolic acid A could mildly inhibit adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (THR)-induced antiplatelet aggregation in a dose-dependent manner, while aspirin played a strong inhibitory effect on AA-induced platelet aggregation in vivo. The effects of salvianolic acid A and aspirin on the coagulation system were similar. At the same time, the results of maximum platelet aggregation rate (MAR) in the rat cerebral ischemia modelMARADP=(41.67±4.55)%, MARAA=(53.22±2.83)%, MARTHR=(73.33±5.04)% indicated that salvianolic acid A could mildly inhibit ADP and AA-induced antiplatelet aggregationMARADP=(26.13±4.60)%, MARAA=(35.53±13.73)%, P<0.01, while aspirin played a strong inhibitory effect on AA-induced platelet aggregationMARAA=(8.13±2.99)%. Salvianolic acid A (10 mg·kg-1) significantly improved the neurological function, cerebral infarction volume(10.77±7.80)% and brain edema(79.72±0.83)% compared with the model group(43.50±12.69)%, (82.25±0.89)% (P<0.01), while the effect of aspirin (100 mg·kg-1) was not obvious. The above results suggest that compared with aspirin, salvianolic acid A provided a mild inhibitory effect on platelet aggregation and protected against cerebral ischemia induced by thrombus. Therefore, salvianolic acid A has a good application prospect in the prevention and treatment of thrombotic diseases.

     

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