药根碱抗大鼠动脉血栓和静脉血栓形成作用的研究

目的:探讨药根碱对大鼠动、静脉血栓形成的作用,并分析其是否会导致出血倾向。方法:采用体外凝血实验,检测药根碱对家兔血浆凝血四项活化部分凝血酶原时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)的影响;采用大鼠FeCl3诱导的颈总动脉血栓模型和下腔静脉结扎静脉血栓模型,检测血栓形成阻塞时间(OT)、血栓重量、凝血、抗凝及纤溶等相关指标,分析药根碱对血栓形成的影响;小鼠尾静脉给药后,测定出血时间,初步分析药根碱是否存在导致出血的风险。结果:①体外实验表明,药根碱在浓度0.4 mg/ml^1.2 mg/ml呈浓度依赖地延长APTT(P<0.01),但不延长PT和TT(P>0.05)。②在大鼠颈总动脉、下腔静脉血栓模型,药根碱2、3 mg/kg静脉注射可显著延长OT(P<0.05或0.01),降低血栓重量(P<0.01);同时药根碱4 mg/kg可显著延长APTT(P<0.05)。但药根碱对PT、TT和血浆血小板、抗凝系统、纤溶系统均无显著影响(P>0.05)。③小鼠尾出血实验表明,药根碱2、4 mg/kg对出血时间均无显著影响(P>0.05)。结论:药根碱具有确切的抗动、静脉血栓的作用,其抗栓作用与血小板、抗凝系统、纤溶系统无显著相关,可能主要通过作用于内源性凝血途径而发挥抗血栓作用。该药不显著延长出血时间,提示其出血副作用较轻。

Anti Artery Thrombosis and Anti Venous Thrombosis Effect of Jateorhizine on Rats

Objective: To investigate the effect of jatrorrhizine on arteriovenous thrombosis in rats, and to analyze its bleeding tendency. Methods: In vitro coagulation test was used to observe the effects of jatrorrhizine on the activated partial thromboplastin time( APTT), prothrombin time(PT) and thrombin time(TT) in rabbit plasma. Then the common carotid artery thrombosis rat model induced by FeCl3 and venous thrombosis model caused by ligating the inferiorvena cava were established to detect thrombosis occlusion time(OT), thrombus weight, coagulation, anticoagulation, fibrinolysis,etc. to analyze the effect of jatrorrhizine on thrombosis. After tail vein injection, the bleeding time of mice was measured to preliminarily analyze the risk of bleeding caused by jatrorrhizine. Results: ①The data of In vitro experiments showed that jatrorrhizine prolonged APTT at the dose of 0.4 mg/ml^1.2 mg/ml, in a concentration-dependent manner(P<0.01), but did not prolong PT and TT(P>0.05). ② In rat models of common carotid artery and inferior vena cava thrombosis, intravenous injection of jatrorrhizine(2,3 mg/kg) significantly prolonged the time of vascular occlusion(P<0.05 or 0.01), it decreased the weight of thrombus(P<0.01), jatrorrhizine at the dose of 4 mg/kg significantly prolonged APTT(P<0.05). However,jatrorrhizine had no significant effect on PT, TT, platelet, anticoagulant system and fibrinolytic system in all groups(P>0.05). ③ The data in the tail hemorrhage test in mice showed that jatrorrhizine(2,4 mg/kg) had no significant effect on the bleeding time(P>0.05). Conclusion: Jatrorrhizine has certain anti-thrombotic effect on arteriovenous thrombosis. Its anti-thrombotic effect has no significant correlation with platelet, anticoagulant system and fibrinolytic system. It may play an anti-thrombotic role by acting on endogenous coagulation pathway. Jatrorrhizine did not significantly prolong the bleeding time, which suggests that the side effects of bleeding is mild.