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目的:探讨新的二氢吡啶钙通道阻滞剂MN9202对实验性血栓形成的影响及其作用机制。方法:采用iv胶原肾上腺素或sc角叉菜胶,分别复制小鼠肺血栓和尾血栓模型。观察MN9202对实验性肺血栓小鼠死亡率,血栓黑尾形成率及微循环的影响。用凝血酶ADP肾上腺素复合诱导剂,复制大鼠脑血栓模型,观察MN9202对大鼠脑血栓损伤的预防作用。结果:MN92024mg·kg-1ip,能明显降低胶原肾上腺素引起的小鼠死亡率(30vs84P<0.01);6mg·kg-1ig,对凝血酶诱导的大鼠脑血栓损伤具有保护作用(0.069±0.068vs0.110±0.013,P<0.01);0.04,0.4mg·kg-1能降低角叉菜胶诱导的血栓黑尾发生率(30,10vs90,P<0.05;P<0.01),明显减轻微血管内皮的渗出,抑制血小板聚集和RBC聚集,改善微血管血流速度。结论:MN9202具有对抗血小板聚集诱导剂及角叉菜胶引起的血栓形成作用。其机制可能与其抑制RBC、血小板聚集,保护血管内皮,舒张痉挛血管有关。
Objective: To investigate the effect of a novel dihydropyridine calcium channel blocker MN9202 on experimental thrombosis and its mechanism. Methods: The model of pulmonary thrombus and tail thrombus was duplicated by iv collagen-epinephrine or sc-carrageenan respectively. To observe the effect of MN9202 on the mortality, the formation rate of black tail and the microcirculation in mice with experimental pulmonary thrombosis. With thrombin ADP adrenergic complex inducer, rat cerebral thrombosis model was duplicated to observe the preventive effect of MN9202 on cerebral thrombosis in rats. Results: MN92024mg · kg-1ip could significantly reduce the death rate of mice induced by collagen epinephrine (30 vs 84P <0.01) and 6 mg · kg-1 ig (P <0.05), and had a protective effect on thrombin-induced cerebral thrombosis .069 ± 0.068vs0.110 ± 0.013, P <0.01); 0.04,0.4mg · kg-1 could reduce the incidence of carrageenan induced black tail (30,10 vs90, P <0.05; P <0.01), significantly reduce the exudation of microvascular endothelial cells, inhibit platelet aggregation and RBC aggregation, improve microvascular blood flow velocity. Conclusion: MN9202 has anti-thrombocyte aggregation-inducing agents and carrageenan-induced thrombosis. The mechanism may be related to its inhibition of RBC, platelet aggregation, protection of vascular endothelium, diastolic spasm blood vessels.