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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,角叉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0.44μmol/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(mm)由24.6±4.6缩短到6.9±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(PT),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-前列腺素F1α(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。
OBJECTIVE: To study the effect and molecular mechanism of the pharmaceutical composition formed by α1 blocker and Ani on thrombosis. Methods: The isolated rat tail artery models were used to investigate the vasodilator effects of the α1-blocker and its drug combination with anisodamine and the carrageenan-induced tail thrombosis in mice to study the effect of the composition on thrombosis And its mechanism. Results: In the α1 blocker, pirarubicin (Pra) had the highest relaxation rate of vascular rings (82.6 ± 8.9%), the strongest effect was EC50 of 0.44μmol / L, and anisodamine and prazosin The composition of the compositions with different dosages, respectively, reduced the carrageenan-induced rat tail thrombus length (mm) from 24.6 ± 4.6 to 6.9 ± 2.7 and the stab insertion rate decreased from 86.6% to 50.0%. The above new pharmaceutical composition can significantly prolong the prothrombin time (PT) of thrombus mice and has no effect on the activated partial thromboplastin time (APTT); can inhibit the activity of tissue-type plasminogen activator (t -PA, 6-keto-PGF1α, and increased PAI-1 and TXB2; Vasodilator effect is further enhanced. Conclusion: The composition of anisodamine and prazosin has the effect of relaxing peripheral blood vessels and improving thrombosis. The anti-thrombotic mechanism is related to the effects of extrinsic coagulation pathway, inhibition of platelet activation and fibrinolysis .