改善血栓形成新的药物组合物及其分子机制

目的：研究α1受体阻断药与山莨菪碱（Ani）形成的药物组合物改善血栓形成的作用及其分子机制。方法：离体大鼠尾动脉血管模型研究α1受体阻断药及其与山莨菪碱的药物组合物的扩血管效应，角又菜胶诱发小鼠尾部血栓模型研究组合物对抗血栓形成的作用及其机制。结果：α1受体阻断药中哌唑嗪（Pra）对血管环舒张率最大，达（82．6±8．9）％，作用强度最强，Ec50值为O．44μmol/L；山莨菪碱和哌唑嗪分别以不同剂量配伍组成组合物，能使角叉菜胶诱发的鼠尾血栓长度（啪）由24．6±4．6缩短到6．94-2．7，成栓率由86．6％下降到50．0％。上述新药物组合物能显著延长血栓小鼠血浆凝血酶原时间（er），对活化部分凝血活酶时间（APTT）无影响；能抑制血栓小鼠血浆中组织型纤溶酶原激活剂（t-PA）、6-酮一前列腺素F1a（6．Keto．PGF1α）含量的降低和组织纤溶酶原激活剂抑制物-1（PAI-1）、血栓烷B2（TXB2）的增多；并不在于扩血管作用的进一步增强上。结论：山莨菪碱和哌唑嗪组成的药物组合物具有舒张外周血管和改善血栓形成的作用，其抗血栓形成机制分别与影响外源性凝血途径、抑制血小板的活化功能以及促进纤溶功能有关。

Novel drug composition ameliorating thrombosis and its molecular mechanisms

Objective： To investigate the antithrombotic effects and its molecular mechanisms of prazosin combined with anisodamine （Ani）. Methods： Isolated rat tail artery rings model was employed to evaluate the vasodilative effects of drugs, mice tail thrombosis model in duced by carrageenan was used to study the antithrombotic effects and its molecular mechanisms of the drug composition. Results： Among αl adrenoreceptor antagonists, prazosin（Pra） had the greatest relaxation rate, which was （82.6± 8.9）%, and the ECso value was 0.44 μmol/L. The drug composition of anisedamine and prazosin of different doses could decrease the length of the tail thrombosis from （24.6 ± 4.6）mm to （6.9 ± 2.7）ram, and the rate of thrombosis was decreased from 86.6% to 50.0%. The drug composition could prolong the prothrombin time （FF） distinctively, but it had no effect on the activated partial thromboplastin time （APTT）. It also could restrain the decrease of serum levels of tissue plasminogen activator （t-PA） and 6- Keto -PGF1α as well as the increase of type 1 plasminogen activator inhibitor （ PAI-1 ） and throm boxane B2（TXB2） in the mice. Conclusion： The drug composition formed by anisodamine and prazosin has good effects of relaxing extremities tiny blood vessels and it can fight against thrombosis, its antithrombotic mechanisms may be related to the influence of the extrinsic coagulation pathway, inhibition of platelet activation functions and the promotion of fibrinolysis function.