银杏叶提取物对4种口服抗凝药抗凝活性的影响

刘志双; 郑玉粉; 孙红娜; 于锋

doi:10.11665/j.issn.1000-5048.20200310

银杏叶提取物对4种口服抗凝药抗凝活性的影响

中国药科大学基础医学与临床药学学院，南京 211198

基金项目: 中国药科大学基本科研业务费资助项目（No. 2632019PY05）

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出版历程
- 收稿日期: 2020-02-18
- 修回日期: 2020-04-29
- 刊出日期: 2020-06-24

Effect of Ginkgo biloba extract on anticoagulation of 4 new oral anticoagulants

Funds: This study was supported by the Basic Research Foundation of China Pharmaceutical University (No. 2632019PY05)

摘要

摘要: 体外研究银杏叶提取物（GBE）对4种新型口服抗凝药（NOACs）达比加群、阿哌沙班、利伐沙班和依度沙班的抗凝活性的影响。分别测定大鼠血浆在不同浓度NOACs、GBE或NOACs联合GBE下的凝血酶时间（TT）、凝血酶原时间（PT）、活化部分凝血酶时间（APTT）和凝血因子Xa（FXa）活性。结果表明在0～500 ng/mL质量浓度范围内，TT、PT和APTT随NOACs浓度增大而延长，除利伐沙班的TT外，其余均具有较好的线性相关性（r²=0.78～0.98）；FXa活性随Xa因子抑制剂（阿哌沙班、利伐沙班和依度沙班）浓度增大而降低，在低浓度范围内（0～250 ng/mL）具有较好的线性相关性（r²=0.85～0.94）。GBE在0～500 μg/mL质量浓度范围内对TT、PT和APTT没有显著影响（P > 0.05），但FXa活性随GBE浓度增大而增强，且具有较好的线性相关性（r² = 0.840 4）。达比加群联合GBE后，TT随GBE浓度增大而延长。上述Xa因子抑制剂联合GBE后，TT随GBE浓度增大而缩短，FXa活性随GBE浓度增大而增强。NOACs联合GBE后的PT、APTT没有显著变化（P > 0.05）。实验结果提示GBE可能协同达比加群的抗凝活性；GBE可能拮抗Xa因子抑制剂的抗凝活性，可能是因为其具有增强FXa活性的作用。
- 银杏叶提取物 /
- 抗凝药 /
- 药物相互作用 /
- 凝血酶时间 /
- 凝血酶原时间 /
- 凝血因子Xa活性
Abstract: To explore the effect of Ginkgo biloba extract (GBE) on anticoagulation of 4 new oral anticoagulants (NOACs), dabigatran, apixaban, rivaroxaban and edoxaban in vitro, thrombin time (TT), prothrombin time (PT), activated partial thrombin time (APTT) and the activity of coagulation factor Xa (FXa) of rat plasma were measured at different concentrations of NOACs, GBE or NOACs combined with GBE, respectively. The results showed that TT, PT and APTT were prolonged with the increase of NOACs concentration in the range of 0-500 ng/mL; that except for TT of rivaroxaban, other results showed a good linear correlation with NOACs concentration (r²= 0.78-0.98); and that FXa activity decreased with increased concentration of FXa inhibitors (apixaban, rivaroxaban and edoxaban), with a good linear correlation with concentration of FXa inhibitors in the range of 0-250 ng/mL (r²= 0.85-0.94). GBE had no significant effect on TT, PT and APTT (P>0.05) in the concentration range of 0-500 μg/mL, but FXa activity had a positive linear correlation with GBE concentration (r²= 0.840 4). TT was prolonged with increasing GBE concentration when dabigatran was combined with GBE. When the above FXa inhibitors were combined with GBE, TT shortened and FXa activity increased with rising GBE concentration. There were no significant changes in PT and APTT (P>0.05) when NOACs were combined with GBE. The study results suggest that GBE may synergize with the anticoagulant activity of dabigatran and antagonize the anticoagulant activity of FXa inhibitors, possibly due to its role in increasing FXa activity.
- Ginkgo biloba extract /
- anticoagulants /
- drug interaction /
- thrombin time /
- prothrombin time /
- factor Xa activity

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